Treatment of amyotrophic lateral sclerosis

Abstract

The disclosure provides methods of treating neurodegenerative conditions, for example, amyotrophic lateral sclerosis, using a regimen of a chlorite salt, for example, sodium chlorite. The long-term survival of subjects receiving sodium chlorite and placebo are compared.

Description

WSGR Docket No. 59077-714.601TREATMENT OF AMYOTROPHIC LATERAL SCLEROSISCROSS REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 695,711, filed on September 17, 2024, andU.S. Provisional Application No. 63 / 773,848, filed March 18, 2025, each of which is entirely incorporated herein by reference.BACKGROUND

[0002] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that destroys motor neurons in the brain and spinal cord. ALS eventually leads to muscle paralysis and death, often within 2-4 years of diagnosis. ALS is a relentlessly progressive and fatal chronic inflammatory neurodegenerative disease primarily characterized by the progressive deterioration of cortical and spinal motor. The loss of motor neurons manifests as muscle weakness leadingto death of most patients within 20-48 monthsafter diagnosis, with the median survival time for patients aged less than 65 years to be about 40 months compared with about 26 months for patients aged > 65 years.INCORPORATION BY REFERENCE

[0003] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.SUMMARY

[0004] In some embodiments, the disclosure provides a method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt.

[0005] In some embodiments, the disclosure provides a method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically-effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in thatWSGR Docket No. 59077-714.601 the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least about 4.8 months, wherein the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0006] In some embodiments, the disclosure provides a method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt.

[0007] In some embodiments, the disclosure provides a method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least 0.05, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.WSGR Docket No. 59077-714.601

[0008] In some embodiments, the disclosure provides a method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least a year.

[0009] In some embodiments, the disclosure provides a method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least about a year, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0010] In some embodiments, the disclosure provides a method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject.

[0011] In some embodiments, the disclosure provides a method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject by spirometry, wherein the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject bodyWSGR Docket No. 59077-714.601 mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0012] In some embodiments, the disclosure provides a method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma neurofilament light chain level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma neurofilament light chain level of the subject, obtaining a second plasma neurofilament light chain level of the subjectbased on a blood assay; d) determining that the second plasma neurofilament light chain level of the subject is a decrease of at least ten percent in comparison to the first plasma neurofilament light chain level of the subject; and e) based at least in part on the determining that the second plasma neurofilament light chain level of the subject is a decrease of at least ten percent in comparison to the first plasma neurofilament light chain level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0013] In some embodiments, the disclosure provides A method comprising increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically - effective regimen of the chlorite salt increases the term of life of the subject, wherein at baseline, the subject demonstrates ALSFRS-R loss of less than 0.5 ALSFRS-Runits / month as determined by respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo -controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high-sensitivity C-reactive protein (hs-CRP) concentration of> 0. 113 mg / dL prior to the placebo-controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo-controlled study estimates overall survival of the study subjects by Kaplan -Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo-controlled study estimates median survival of: i) 29 months for all study subjects receiving placebo and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-RWSGR Docket No. 59077-714.601 units / month as determined by respirometry; and ii) 48 months for all study subjects receiving 2 mg / kg sodium chlorite based on chlorite ion and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry.

[0014] In some embodiments, the disclosure provides a method comprising increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically - effective regimen of the chlorite salt increases the term of life of the subject, wherein at baseline, the subject demonstrates ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo -controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high-sensitivity C-reactive protein (hs-CRP) concentration of> 0. 113 mg / dL prior to the placebo-controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo-controlled study estimates overall survival of the study subjects by Kaplan -Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo-controlled study estimates median survival of: i) 29 months for all study subjects receiving placebo and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry; and ii) 42 months for all study subjects receiving 2 mg / kg sodium chlorite based on chlorite ion and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry.

[0015] In some embodiments, the disclosure provides a method comprising reducing vital capacity loss of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt reduces vital capacity loss of the subject, wherein at baseline, the subject demonstrates greater than 80% vital capacity and ALSFRS-R loss of less than 0.57 ALSFRS-R units / month as determined by respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, whereinWSGR Docket No. 59077-714.601 the study subjects were enrolled in the placebo-controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high -sensitivity C-reactive protein (hs-CRP) concentration of > 0.113 mg / dL prior to the placebo-controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo -controlled study estimates overall survival of the study subjects by Kaplan-Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo- controlled study estimates that the study subjects demonstrate a slowing of 43% to 55% of loss of vital capacity compared to the subjects receiving placebo as determined by respirometry.

[0016] In some embodiments, the disclosure provides a method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma IL-18 level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma IL-18 level of the subject, obtaining a second IL-10 level of the subject based on a blood assay; d) determining that the second plasma IL-18 level of the subject is a decrease of at least ten percent in comparison to the first plasma IL-18 level of the subject; and e) based at least in part on the determining that the second plasma IL-18 level of the subject is a decrease of at least ten percent in comparison to the first plasma IL-18 level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0017] In some embodiments, the disclosure provides a method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma HGF level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma HGF level of the subject, obtaining a second plasma HGF level of the subject based on a blood assay; d) determining that the second plasmaHGF level of the subject is a decrease of at least ten percent in comparison to the first plasma HGF level of the subject; and e) based at least in part on the determining that the second plasmaHGF level of the subject is a decrease of at least ten percentWSGR Docket No. 59077-714.601 in comparison to the first plasma HGF level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0018] In some embodiments, the disclosure provides a method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma sCD163 level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma sCD163 level of the subject, obtaining a second plasma sCD163 level of the subject based on a blood assay; d) determining that the second plasma sCD163 level of the subject is a decrease of at least ten percent in comparison to the first plasma sCD163 level of the subject; and e) based at least in part on the determining that the second plasma sCD163 level of the subject is a decrease of at least ten percent in comparison to the first plasma sCD163 level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0019] In some embodiments, the disclosure provides a method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma LPS level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma LPS level of the subject, obtaining a second plasma LPS level of the subject based on a blood assay; d) determining that the second plasma LPS level of the subj ect is a decrease of at least ten percent in comparison to the first plasma LPS level of the subject; and e) based at least in part on the determining that the second plasmaLPS level of the subject is a decrease of at least ten percent in comparison to the first plasma LPS level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.BRIEF DESCRIPTION OF THE DRAWINGS

[0020] FIG. 1 illustrates pathogenesis of ALS.

[0021] FIG. 2 illustrates the same pathway when treated with Compound 1 (sodium chlorite).

[0022] FIG. 3 shows a Kaplan-Meier curve of survival probability for subjects who received sodium chlorite at a dose of 2 mg / kg subject body weight of the compound based on mass of chlorite ion compared with placebo.

[0023] FIG. 4 shows a Kaplan-Meier curve of survival probability for subjects who received sodium chlorite at a dose of 2 mg / kg subject body weight (or mass) of the compound based on mass of chlorite ion compared with placebo, with the therapy beginning when the patients were < 65 years old.

[0024] FIG. 5 shows a Kaplan-Meier curve of survival probability for subjects who receivedWSGR Docket No. 59077-714.601 sodium chlorite at a dose of 1 mg / kg subject body weight (or mass) of the compound based on mass of chlorite ion compared with placebo, with the therapy beginning when the subjects were < 65 years old.

[0025] FIG. 6 shows the effectiveness of sodium chlorite at a dose of 2 mg / kg subject body weight in all enrolled subjects, with the therapy beginning when the subjects were < 65 years old.

[0026] FIG. 7 provides a high-level summary of the phase 2A trail with subjects receiving sodium chlorite over a 6 -month treatment period.

[0027] FIG. 8 shows a distribution of baseline creatinine levels in Phase 2 subjects.

[0028] FIGs. 9-10 show changes in baseline creatinine levels over a 6 -month treatment period following treatment with sodium chlorite.

[0029] FIG. 11 shows the effect of sodium chlorite treatment in subjects under 65 years of age with baseline serum creatinine < 60 pM / L.

[0030] FIG. 12 shows a Kaplan-Meier curve of survival probability for subjects with baseline serum creatinine treated with sodium chlorite.

[0031] FIGs. 13A-13C illustrates a model of ALS pathogenesis as being an immune activation disorder with ALS initiation at the neuromuscular junction.

[0032] FIG. 14 shows a Kaplan-Meier curve of survival probability for Phase 2 subjects who completed the trial treated with 2 mg / kg sodium chlorite.

[0033] FIG. 15 shows a Kaplan-Meier curve of survival probability for Phase 2 subjects who completed the trial treated with 2 mg / kg sodium chlorite or placebo with baseline C-Reactive Protein (CRP) levels greater than 1.13 mg / L.

[0034] FIG. 16 shows the change in vital capacity from baseline in Phase 2 trial subjects who completed the trial treated with 2 mg / kg sodium chlorite or placebo with baseline CRP levels > 1.13 mg / L.

[0035] FIG. 17 shows baseline creatinine distributions in subjects with low and high baseline creatinine and baseline CRP > 1.13 mg / L.

[0036] FIG. 18 shows the change in vital capacity over time in subjects with low creatinine levels treated with sodium chlorite or placebo.

[0037] FIG. 19 shows the change in vital capacity over time in subjects with high creatinine levels treated with sodium chlorite or placebo.

[0038] FIG. 20 shows a Kaplan-Meier curve of survival probability for subjects with low creatinine levels and baseline plasma CRP > 1.13 mg / L treated with sodium chlorite or placebo.

[0039] FIG. 21 shows a Kaplan-Meier curve of survival probability for subjects with high creatinine levels and baseline plasma CRP > 1.13 mg / L treated with sodium chlorite or placebo.WSGR Docket No. 59077-714.601

[0040] FIG. 22 shows a simple schematic of the innate immune self -regulatory cycle.

[0041] FIG. 23 shows the effect of sodium chlorite treatment on biomarker levels in non- progressor subjects.

[0042] FIG. 24 shows a time to event analysis for a predicted loss of 15% vital capacity or death for subjects treated with sodium chlorite or placebo.

[0043] FIG. 25 shows a Kaplan-Meier curve of survival probability over 6-months of treatment with sodium chlorite.

[0044] FIG. 26 summarizes characteristics of high-sensitive C-Reactive Protein (CRP), serum creatinine, and age for gauging sodium chlorite’s response in ALS.

[0045] FIG. 27 shows the change in vital capacity in subjects with baseline hsCRP > 1.13 mg / L and age between 40-65 treated with sodium chlorite or placebo.

[0046] FIGs. 28-29 show 11 -year overall survival in subjects treated with sodium chlorite and placebo.

[0047] FIGs. 30-32 show Kaplan-Meier curves of survival probability for subjects treated with sodium chlorite and placebo stratified by hsCRP and creatinine biomarkers.

[0048] FIGs. 33-35 show changes in vital capacity over 6-months of treatment in subjects treated with sodium chlorite and placebo stratified by hsCRP and creatinine biomarkers.

[0049] FIG. 36 illustrates a dosing regimen for sodium chlorite.

[0050] FIG. 37 shows a Kaplan-Meier curve of event free survival, assessing the time to loss of 15% predicted vital capacity in subjects treated with sodium chlorite and placebo.

[0051] FIG. 38 shows a quantification of the incidence of 15% loss of predicted vital capacity (pVC) events in the placebo and sodium chlorite -treated populations.

[0052] FIG. 39 shows time to event analysis for 15% pVC loss in Phase 2A subjects with symptom onset less than 3 years before treatment treated with sodium chlorite and placebo.

[0053] FIG. 40 shows time to event analysis for 15% pVC loss in Phase 2D subjects with plasma CRP > 1.13 mg / L before treatment treated with sodium chlorite and placebo.

[0054] FIG. 41 shows the effect of pVC loss of 15% on survival in sodium chlorite -treated subjects.

[0055] FIG. 42 shows the proportion of 15% pVC loss in subjects with bulbar onset ALS treated with sodium chlorite or placebo.

[0056] FIG. 43 shows the change in ALSFRS-R overtime in bulbar onset ALS subjects treated with sodium chlorite or placebo.

[0057] FIG. 44 shows a Kaplan-Meier curve of survival probability for subjects with bulbar onset ALS treated with sodium chlorite or placebo.

[0058] FIG. 45 shows the rate of non-progression of subject in Phase 2 trials with an innateWSGR Docket No. 59077-714.601 immune activation phenotype treated with sodium chlorite or placebo.

[0059] FIG. 46 shows a Kaplan-Meier curve of survival probability for non-progressing subject with CRP > 1.13 mg / L and age < 65 treated with sodium chlorite or placebo.

[0060] FIG. 47 shows a Kaplan-Meier curve of survival probability for subjects with CRP>1.13 mg / L and age < 65 treated with sodium chlorite or placebo.

[0061] FIG. 48 shows a Kaplan-Meier curve of survival probability for non -progressing subjects treated with sodium chlorite or placebo.

[0062] FIG. 49 shows a Kaplan-Meier curve of survival probability for non-progressing subjects with CRP > 3 mg / L or CRP between 1 -3 mg / L treated with sodium chlorite or placebo.

[0063] FIG. 50 shows a Kaplan-Meier curve of survival probability for non -progressing subjects with CRP > 3 mg / L treated with sodium chlorite or placebo.

[0064] FIG. 51 illustrates the response rate of non -progressing subjects with CRP > 3 mg / L treated with sodium chlorite or placebo.

[0065] FIG. 52 shows time to event (TTE) analysis for subjects to lose 15% pVC over the 6- month treatment period for subjects with CRP > 3 mg / L treated with sodium chlorite or placebo.

[0066] FIG. 53 shows the change in ALSFRS-R from baseline over time for sodium chlorite and placebo-treated subjects with CRP > 3 mg / L.

[0067] FIG. 54 shows a Kaplan-Meier curve of survival probability for sodium chlorite- and placebo-treated subjects with CRP > 3 mg / L.

[0068] FIG. 55 illustrates a Phase 3 trial design.

[0069] FIG. 56 shows the effect of sodium chlorite treatment on ALSFRS-R rating in moderately progressing ALS.

[0070] FIG. 57 shows a Kaplan-Meier curve of survival probability for subjects with ALSFRS- R loss of less than 0.5 ALSFRS-R units / month treated with sodium chlorite or placebo.

[0071] FIG. 58 shows a Kaplan-Meier curve of survival probability for subjects with ALSFRS- R loss greater than 0.5 ALSFRS-R units / month treated with sodium chlorite or placebo.

[0072] FIG. 59 shows the change in vital capacity in moderately progressing ALS subjects with ALSFRS-R loss less than 0.5 units / month treated with sodium chlorite or placebo.

[0073] FIG. 60 shows a change in vital capacity from baseline for ALS subjects with a disease progression rate greater than 0.5 ALSFRS-R units lost / month treated with sodium chlorite or placebo.

[0074] FIG. 61 shows a change in ALSFRS-R from baseline for subjects with moderately progressing ALS subjects treated with sodium chlorite or placebo.

[0075] FIG. 62 shows a change in ALSFRS-R from baseline for ALS subjects with a disease progression rate greater than 0.5 ALSFRS-R units lost / month treated with sodium chlorite orWSGR Docket No. 59077-714.601 placebo.

[0076] FIG. 63 shows a Kaplan-Meier curve of survival probability for subjects with a disease progression rate less than 0.5 units of ALSFRS-R lost / month treated with sodium chlorite or placebo.

[0077] FIG. 64 shows the effect of sodium chlorite treatment on disease progression in subjects with >80% vital capacity at baseline and a disease progression rate of <0.57 units ALSFRS-R lost / month.

[0078] FIG. 65 shows the change in vital capacity from baseline for subjects with >80% vital capacity atbaseline and a disease progression rate of <0.57 units ALSFRS-R lost / month treated with sodium chlorite or placebo.

[0079] FIG. 66 illustrates a proposed model of neuronal death in ALS based on neurofilament light chain (NfL) levels.

[0080] FIG. 67 shows the change in % vital capacity from baseline over time for subjects with low plasma NfL and a disease progression rate of less than 0.5 units of ALSFRS-R lost / month treated with sodium chlorite or placebo.

[0081] FIG. 68 shows the change in % vital capacity from baseline over time for subjects with low plasma NfL and a disease progression rate of greater than 0.5 units of ALSFRS-R lost / month treated with sodium chlorite or placebo.

[0082] FIG. 69 shows the change in predicted vital capacity from baseline for Phase 2A subjects treated with sodium chlorite and placebo with slow disease progression

[0083] FIG. 70 shows the change in predicted vital capacity from baseline for Phase 2A subjects with NfL levels less than the median value treated with sodium chlorite or placebo.

[0084] FIG.71 shows the effect of sodium chlorite treatment on disease progression in Phase 2A subjects with NfL levels less than the median value.

[0085] FIG. 72 shows a Kaplan-Meier curve of survival probability for Phase 2A subjects with a NfL level less than the median value treated with sodium chlorite or placebo.

[0086] FIG. 73 shows a Kaplan-Meier curve of survival probability for Phase 2A subjects with a NfL level greater than the median value treated with sodium chlorite or placebo.

[0087] FIGs. 74A-B illustrates a correlation between baseline NfL and ALSFRS-R change from baseline.

[0088] FIG. 75 shows the change in NfL levels from baseline in subjects with a disease progression rate of less than 0.5 units of ALSFRS-R lost / month treated with sodium chlorite or placebo.

[0089] FIG. 76 shows IL-18 levels in subjects that responded to sodium chlorite and in subjects that did not responseWSGR Docket No. 59077-714.601

[0090] FIG. 77 illustrates a correlation between baseline IL-18 levels and wide-range C- Reactive Protein (wrCRP).

[0091] FIG. 78 shows the change in creatinine levels from baseline for subjects with a disease progression rate of less than 0.5 units ALSFRS-R lost / month.

[0092] FIG. 79 shows the change in creatinine levels from baseline for subjects with a disease progression rate greater than 0.5 units ALSFRS-R lost / monthDETAILED DESCRIPTION OF THE INVENTION

[0093] Described herein are methods of increasing life expectancy and survival probability in subjects having a condition by administering to the subject a chlorite salt, for example, sodium chlorite. The condition can be a neurodegenerative condition, for example, amyotrophic lateral sclerosis (ALS). By receiving a regimen of the chlorite salt as described herein, the subject has a likelihood of experiencing an increased life expectancy and an increased survival probability in comparison to not having taken the regimen, or in comparison to an analogous person who is identical to the subject in all ways other than that the analogous persons did not receive the regimen.

[0094] Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a fatal neurodegenerative disease associated with inappropriate immune system dysfunction involving NF-kB activation, proinflammatory factor production, and progressive changes in motor neuron function. Factors elaborated by spinal cord microglia both damage and inhibit repair of neurons injured by the accumulation of misfolded proteins. Inflammation and immune system dysregulation are involved in the progression of ALS, including the presence of activated macrophages in ALS patients. Compounds that can reduce inflammation and immune system dysregulation, possibly by returning macrophages to their inactivated state, can be effective in treating ALS or other disorders with immune system dysfunction.

[0095] Macrophages are white blood cells produced by the division of monocytes, which play a role in innate immunity (non-specific immune defenses) and help to initiate adaptive immunity (specific defense mechanisms). The cells phagocytose (i.e., engulf and then digest) cellular debris and pathogens either as stationary or as mobile cells. When activated by pathogens or other mechanisms, macrophages stimulate and recruit lymphocytes and other immune cells to respond. Activated macrophages are involved in the progression of several diseases and disorders, including amyotrophic lateral sclerosis (ALS). Activated macrophages elicit massive leukocyte infiltration and flood surrounding tissue with inflammatory mediators, pro-apoptotic factors, and matrix degrading proteases. These actions can result in inflammation that can dismantle tissues to the point of inflicting serious injury. Tissue destruction perpetrated byWSGR Docket No. 59077-714.601 macrophage-induced inflammation, a form of immune system dysregulation, can be associated with the progression of the degenerative disease ALS.

[0096] ALS patients can be defined by four generalized patient groups: slowly progressive, fast progressive, early disease presentation, and late disease presentation. Of the four categories, only the slowly progressive patient group includes inflammation as a significant aspect of ALS disease pathology. The slowly progressive subset’s association with inflammation is inferred upon study of ALS in association with C-reactive protein (CRP) levels overtime from diagnosis. The longer an ALS patient lives after diagnosis, the higher the plasma CRP. A large subgroup of ALS patients is evidence for ongoing, and potentially growing, inflammation associated with a slower rate of progression. Methods of identifying ALS patients with inflammation are needed to treat such ALS patients with targeted immune regulating therapies.

[0097] ALS can also be distinguished by ALS symptoms, genetic cause, lack of clear genetic association, or combinations thereof. In some embodiments, subjects with ALS can be categorized as sporadic or inherited ALS. Sporadic ALS pathology occurs in subjects with no genetic or family history of ALS, while inherited ALS pathology occurs in subjects with a genetic or family history of ALS. As many as 90% to 95% of ALS cases can be sporadic and occur in subjects with no genetic or family history of ALS.

[0098] Mutations to one or more genes can be associated with subjects experiencing either an inherited or sporadic ALS pathology. For instance, 60% of individuals with familial ALS can have an identified genetic mutation to one or more genes associated with the condition. In some embodiments, subjects experiencing either an inherited ALS pathology have inherited mutations to one or more of the genes listed in TABLE 1. Mutations in the C9orf72 gene account for 30% to 40% of inherited ALS in the United States and Europe; worldwide SOD1 gene mutations cause 15% to 20% of inherited ALS; and TARDBP and FUS gene mutations each account for about 5% of cases of inherited ALS.

[0099] In some embodiments, mutations to one or more genes listed in TABLE 1 can be important to the normal functioning of motor neurons and other cells, and mutations to one or more of these genes can contribute to the decline in function or death of motor neurons in ALS patients. In some embodiments, mutations to one or more genes of TABLE 1 can contribute to a decline in motor neutron function or neuron death as a result of buildup of protein aggregates in motor neurons, a slowing in the transport of materials needed for the proper function of axons in motor neurons, an accumulation of toxic substances in the motor neurons, or combinations thereof.TABLE 1Gene Associated with ALSWSGR Docket No. 59077-714.601WSGR Docket No. 59077-714.601

[0100] Initial events of ALS pathogenesis occur at the neuromuscular junction where neuron axonal processes interact with muscle out-side the central nervous system. This reaction is inflammatory and is mediated by components of the innate immune system including acute phase reactant proteins and blood derived granulocytes and macrophages. The triggering events can be linked to the presence of abnormally folded or aggregated proteins associated with ALS such as TDP43 and SOD-1, recognized by the innate immune system within the neuromuscular junction. Normally, the acute phase reaction is followed closely by immune signals that turn off that reaction to have the immune system remain in balance. Therefore, the plasma based or humoral innate immune system provides feedback on activated macrophages, the cellular drivers of inflammation and balance the inflammatory with anti-inflammatory immune signals. Proteins associated with the acute phase innate immune response can be measured in the blood and one, C-reactive protein (CRP), allows quantitative determination of the degree of inflammation associated with disease.

[0101] Plasma CRP levels are acutely elevated more than 30 -fold in an acute phase reaction, but rapidly fall as the initiator of the inflammation becomes controlled. Two categories of insult cause the synthesis of CRP predominantly from the liver: infection and tissue damage. Infections can trigger both the innate and the adaptive response so that blood levels of factors produced by both immune reactions are present in the plasma. Although CRP rapidly appears after an insult and is viewed as a marker for inflammation severity, the general function is to facilitate phagocytic cell clearance of foreign material. In addition, CRP down regulates otherWSGR Docket No. 59077-714.601 proinflammatory components of the innate immune response to turn down the production of inflammatory by-products. Therefore, if CRP levels are chronically elevated, then ongoing infectious or tissue damaging processes are possibly driving the persistent CRP response.Continued tissue damage absent the persistence of an acute phase process suggests uncoupling of the innate immune response to signals that normally drive that reaction.

[0102] Other plasma factors involved in innate immune response include serum amyloid A (SAA), levels of which increase in parallel with CRP. SAA binds to and clears bacterial byproducts such as lipopolysaccharide (LPS). Alpha 2 macroglobulin (A2M) becomes activated when the acute phase reaction is initiated and clears by-products of damaged cells, specifically proteases. When further activated by hypochlorite, a byproduct of the oxidative burst reaction initiated by phagocyte (granulocytes, macrophages) activation, A2M forms a dimer, releases preformed TGFB1, and binds to and removes misfolded proteins and aggregates.

[0103] The innate immune system responds rapidly to infection and / or tissue damage. Within minutes, the acute phase reactants CRP and serum amyloid A (SAA) increase more than 30 -fold in plasma. When an inflammatory response is initiated, byproducts of that response need to be removed or neutralized to avoid significant tissue damage. CRP facilitates the clearance of dead cells and protein aggregates. SAA binds to and removes products of bacterial clearance mediated by activated phagocytes such as LPS.

[0104] TGFB1 is a potent regulator of inflammation and down regulates inflammatory drive. Together, CRP, SAA, and A2M represent major humoral components of the innate immune system and coordinate to regulate the degree of inflammatory reactions associated with the activated cellular components of the response (macrophages, granulocytes).

[0105] Sodium chlorite can augment the innate immune activation cycle in ALS patients with elevated baseline plasma CRP. The innate immune activation cycle is a self -regulated process that occurs after the immune system is exposed to infection or tissue damage. The initiator of immune system activation can be the presence of misfolded or aggregated proteins, including TDP43.

[0106] In response to immune system activation, blood derived macrophages undergo oxidative burst and release hypochlorous acid as a byproduct. The acute phase response involves elevation of CRP and SAA. CRP facilitates clearance of damaged cells and tissues. SAA binds to and clears bacterial byproducts, including LPS. A2M is activated to remove damaged cell products, including proteases. Hypochlorous acid stimulates the production of taurine chloramine (TauCl) and promotes dimerization of A2M. A2M dimers clear misfolded proteins and release pre-synthesized TGFB1 to feedback on proinflammatory cells and turn off NFkB. Sodium chlorite is converted in vivo to HC1O and stimulates dimerization of A2M andWSGR Docket No. 59077-714.601 subsequent release of pre-synthesized TGFB1.Methods

[0107] In some embodiments, disclosed herein is a pharmaceutical composition for use in treating a condition, for example, chronic obstructive pulmonary disease (COPD), or colitis.

[0108] Disclosed herein are compositions and methods for treating neurodegenerative diseases. Non-limiting examples of neurodegenerative diseases include dementia, amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Alzheimer’s disease, vascular dementia, Parkinson’s disease, multiple sclerosis, primary progressive multiple sclerosis, chronic obstructive pulmonary disease (COPD), colitis, Lewy Body Dementia, frontotemporal dementia, and dementia associated with Down Syndrome. In some embodiments, the neurodegenerative disease is ALS. In some embodiments, the neurodegenerative disease is Alzheimer’s disease. In some embodiments, the neurodegenerative disease is Parkinson’s disease. Treatments can include, for example, a formulation of a compound that is converted to taurine chloramine in vivo in a human, for example, a chlorite salt, for example, sodium chlorite.

[0109] In some embodiments, the method further comprises recommending that the subject undergo the therapy for the ALS based on the determining that the subject is eligible for the therapy for the ALS.

[0110] A subject for a therapy herein canbe of any suitable age, for example, at least 30 years old, at least 35 years old, at least 40 years old, at least 45 years old, at least 50 years old, at least 55 years old, atleast 60 years old, 40 to 80 years old, 40 to 75 years old, 40 to 70 years old, 40 to 65 years old, 40 to 60 years old, 40 to 55 years old, 40 to 50 years old, no greater than 80 years old, no greater than 75 years old, no greater than 70 years old, no greater than 65 years old, or no greater than 60 years old.

[0111] A subject described herein can be of any suitable age. In some embodiments, the subject is at least age 40, at least age 41, at least age 42, at least age 43, at least age 44, at least age 45, at least age 46, at least age 47, at least age 48, at least age 49, at least age 50, at least age 51 , at least age 52, atleast age 53, at least age 54, atleast age 55, atleast age 56, at least age 57, at least age 58, atleast age 59, at least age 60, at least age 61, at least age 62, at least age 63, at least age 64, or atleast age 65. In some embodiments, the subject is at least age 40, at least age 41, at least age 42, atleast age 43, at least age 44, atleast age 45, atleast age 46, at least age 47, at least age 48, at least age 49, or at least age 50. In some embodiments, the subject is at least age 51, atleast age 52, at least age 53, at least age 54, atleast age 55, at least age 56, at least age 57, at least age 58, atleast age 59, at least age 60, atleast age 61, atleast age 62, at least age 63, at least age 64, or at least age 65. In some embodiments, the subject is at least age 40. In someWSGR Docket No. 59077-714.601 embodiments, the subject is at least age 41. In some embodiments, the subject is at least age 42. In some embodiments, the subject is at least age 43. In some embodiments, the subject is at least age 44. In some embodiments, the subject is at least age 44. In some embodiments, the subject is at least age 45. In some embodiments, the subject is at least age 46. In some embodiments, the subject is at least age 47. In some embodiments, the subject is at least age 48. In some embodiments, the subject is at least age 49. In some embodiments, the subject is at least age 50. In some embodiments, the subject is at least age 51. In some embodiments, the subject is at least age 52. In some embodiments, the subject is at least age 53. In some embodiments, the subject is at least age 54. In some embodiments, the subject is at least age 55. In some embodiments, the subject is at least age 56. In some embodiments, the subject is at least age 57. In some embodiments, the subject is at least age 58. In some embodiments, the subject is at least age 59. In some embodiments, the subject is at least age 60. In some embodiments, the subject is at least age 61. In some embodiments, the subject is atleast age 62. In some embodiments, the subject is at least age 63. In some embodiments, the subject is at least age 64. In some embodiments, the subject is at least age 65.

[0112] In some embodiments, the subject is no greater than age 40, no greater than age 41, no greater than age 42, no greater than age 43, no greater than age 44, no greater than age 45, no greater than age 46, no greater than age 47, no greater than age 48, no greater than age 49, no greater than age 50, no greater than age 51, no greater than age 52, no greater than age 53, no greater than age 54, no greater than age 55, no greater than age 56, no greater than age 57, no greater than age 58, no greater than age 59, no greater than age 60, no greater than age 61, no greater than age 62, no greater than age 63, no greater than age 64, or no greater than age 65. In some embodiments, the subject is no greater than age 41, no greater than age 42, no greater than age 43, no greater than age 44, no greater than age 45, no greater than age 46, no greater than age 47, no greater than age 48, no greater than age 49, or no greater than age 50. In some embodiments, the subject is no greater than age 51 , no greater than age 52, no greater than age 53, no greater than age 54, no greater than age 55, no greater than age 56, no greater than age 57, no greater than age 58, no greater than age 59, no greater than age 60, no greater than age 61, no greater than age 62, no greater than age 63, no greater than age 64, or no greater than age 65. In some embodiments, the subject is no greater than age 40. In some embodiments, the subject is no greater than age 41 . In some embodiments, the subject is no greater than age 42. In some embodiments, the subject is no greater than age 43. In some embodiments, the subject is no greater than age 44. In some embodiments, the subject is no greater than age 44. In some embodiments, the subject is no greater than age 45. In some embodiments, the subject is no greater than age 46. In some embodiments, the subject is no greater than age 47. In someWSGR Docket No. 59077-714.601 embodiments, the subject is no greater than age 48. In some embodiments, the subject is no greater than age 49. In some embodiments, the subject is no greater than age 50. In some embodiments, the subject is no greater than age 51. In some embodiments, the subject is no greater than age 52. In some embodiments, the subject is no greater than age 53. In some embodiments, the subject is no greater than age 54. In some embodiments, the subject is no greater than age 55. In some embodiments, the subject is no greater than age 56. In some embodiments, the subject is no greater than age 57. In some embodiments, the subject is no greater than age 58. In some embodiments, the subject is no greater than age 59. In some embodiments, the subject is no greater than age 60. In some embodiments, the subject is no greater than age 61 . In some embodiments, the subject is no greater than age 62. In some embodiments, the subject is no greater than age 63. In some embodiments, the subject is no greater than age 64. In some embodiments, the subject is no greater than age 65.

[0113] In some embodiments, the subject is about age 40, about age 41, about age 42, about age 43, about age 44, about age 45, about age 46, about age 47, about age 48, about age 49, about age 50, about age 51, about age 52, about age 53, about age 54, about age 55, about age 56, about age 57, about age 58, about age 59, about age 60, about age 61, about age 62, about age 63, about age 64, or about age 65. In some embodiments, the subject is about age 40, about age 41, about age 42, about age 43, about age 44, about age 45, about age 46, about age 47, about age 48, about age 49, or about age 50. In some embodiments, the subject is about age 51, about age 52, about age 53, about age 54, about age 55, about age 56, about age 57, about age 58, about age 59, about age 60, about age 61, about age 62, about age 63, about age 64, or about age 65. In some embodiments, the subject is about age 40. In some embodiments, the subject is about age 41. In some embodiments, the subject is about age 42. In some embodiments, the subject is about age 43. In some embodiments, the subject is about age 44. In some embodiments, the subject is about age 44. In some embodiments, the subject is about age 45. In some embodiments, the subject is about age 46. In some embodiments, the subject is about age 47. In some embodiments, the subject is about age 48. In some embodiments, the subject is about age 49. In some embodiments, the subject is about age 50. In some embodiments, the subject is about age 51 . In some embodiments, the subject is about age 52. In some embodiments, the subject is about age 53. In some embodiments, the subject is about age 54. In some embodiments, the subjectis about age 55. In some embodiments, the subject is about age 56. In some embodiments, the subject is about age 57. In some embodiments, the subject is about age 58. In some embodiments, the subject is about age 59. In some embodiments, the subject is about age 60. In some embodiments, the subject is about age 61 . In some embodiments, the subjectis about age 62. In some embodiments, the subject is about age 63. InWSGR Docket No. 59077-714.601 some embodiments, the subject is about age 64. In some embodiments, the subject is about age 65.

[0114] In some embodiments, the subject has a neurodegenerative disease. In some embodiments, the subject has ALS. In some embodiments, the subject has Alzheimer’s disease. In some embodiments, the subject has Parkinson’s disease.

[0115] In some embodiments, the subject possesses a CRP level greater than 1.13 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 1.15 mg / L as determined by a blood assay. In some embodiments, the subject pos sesses a CRP level greater than 1.17 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 1.2 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 1.5 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 2 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 2.5 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 3 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 3.5 mg / L as determined by a blood assay. In some embodiments, the subject possesses a CRP level greater than 4 mg / L as determined by a blood assay. Non-limiting methods of screening patient CRP levels include latex agglutination, latex- enhanced nephelometry, photometric measurement of antigen -antibody reaction, and highly sensitive Near Infrared Particle Immunoassay rate methodology.

[0116] In some embodiments, the subject is administered an amount of a compound that is converted to taurine chloramine in vivo in a human, for example, a chlorite salt, for example, sodium chlorite. In some embodiments, the subject is administered an amount of a compound that is converted to taurine chloramine in vivo in a human, for example, a chlorite salt, for example, sodium chlorite, that is therapeutically effective for a neurodegenerative disease, a mental health condition, or a condition associated with aging. In some embodiments, the subject is administered an amount of a compound that is converted to taurine chloramine in vivo in a human, for example, a chlorite salt, for example, sodium chlorite, that is therapeutically effective for ALS.

[0117] In some embodiments, the amount is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is about 0.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is about 1.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is about 1.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is about 2.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is about 2.5 mg / kg / day to about 3.5 mg / kg / day. In someWSGR Docket No. 59077-714.601 embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0118] In some embodiments, the amount is about 1.0 mg / kg / day to about 10 mg / kg / day. In some embodiments, the amount is about 2.0 mg / kg / day to about 10 mg / kg / day. In some embodiments, the amount is about 3.0 mg / kg / day to about 10 mg / kg / day. In some embodiments, the amountis about4.0 mg / kg / day to about 10 mg / kg / day. In some embodiments, the amount is about 5.0 mg / kg / day to about 10 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0119] In some embodiments, the amount is about 0.2 mg / kg / day . In some embodiments, the amountis about 0.5 mg / kg / day. In some embodiments, the amount is about 1.0 mg / kg / day. In some embodiments, the amount is about 1.2 mg / kg / day. In some embodiments, the amount is about 1.4 mg / kg / day. In some embodiments, the amount is about 1.6 mg / kg / day. In some embodiments, the amount is about 1.8 mg / kg / day. In some embodiments, the amount is about 2.0 mg / kg / day. In some embodiments, the amount is about 2.2 mg / kg / day. In some embodiments, the amount is about 2.4 mg / kg / day. In some embodiments, the amount is about 2.6 mg / kg / day. In some embodiments, the amount is about 2.8 mg / kg / day. In some embodiments, the amount is about 3.0 mg / kg / day. In some embodiments, the amount is about 3.2 mg / kg / day. In some embodiments, the amount is about 3.5 mg / kg / day. In some embodiment, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0120] In some embodiments, the amount is about 4.0 mg / kg / day. In some embodiments, the amountis about 5.0 mg / kg / day. In some embodiments, the amount is about 6.0 mg / kg / day. In some embodiments, the amount is about 7.0 mg / kg / day. In some embodiments, the amount is about 8.0 mg / kg / day. In some embodiments, the amount is about 9.0 mg / kg / day. In some embodiments, the amount is about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion .

[0121] In some embodiments, the administering is oral. In some embodiments, the administering is parenteral. In some embodiments, the administering is intravenous.

[0122] In some embodiments, the subject is on a regimen of a compound that is converted to taurine chloramine in vivo in a human, for example, sodium chlorite. In some embodiments, the regimen of sodium chlorite is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 0.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1 .0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.5WSGR Docket No. 59077-714.601 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0123] In some embodiments, the regimen of sodium chlorite is about 1.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 3.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 4.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 5.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0124] In some embodiments, the regimen of sodium chlorite is about 0.2 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 0.5 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.2 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.4 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.6 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 1.8 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.2 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.4 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.6 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 2.8 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 3.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 3.2 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 3.5 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0125] In some embodiments, the regimen of sodium chlorite is about 4.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 5.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 6.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 7.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 8.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 9.0 mg / kg / day. In some embodiments, the regimen of sodium chlorite is about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0126] In some embodiments, the regimen is administered orally. In some embodiments, theWSGR Docket No. 59077-714.601 regimen is administered parenterally. In some embodiments, the regimen is administered intravenously.

[0127] In some embodiments, the subject is undergoing a treatment for ALS, wherein the treatment is a therapeutic regimen of a compound that is converted to taurine chloramine in vivo in a human, for example, sodium chlorite. In some embodiments, the method further comprises determiningto discontinue the therapeutic regimen. In some embodiments, the method further comprises determining to continue the therapeutic regimen.

[0128] In some embodiments, the therapeutic regimen is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 0.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0129] In some embodiments, the therapeutic regimen is about 1.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 3.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 4.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 5.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0130] In some embodiments, the therapeutic regimen is about 0.2 mg / kg / day. In some embodiments, the therapeutic regimen is about 0.5 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.2 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.4 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.6 mg / kg / day. In some embodiments, the therapeutic regimen is about 1.8 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.2 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.4 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.6 mg / kg / day. In some embodiments, the therapeutic regimen is about 2.8 mg / kg / day. In some embodiments, the therapeutic regimen is about 3.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 3.2 mg / kg / day. In some embodiments, the therapeutic regimen is about 3.5 mg / kg / day. In some embodiments, the amount is based onWSGR Docket No. 59077-714.601 subject body weight (or mass) of the compound based on mass of chlorite ion.

[0131] In some embodiments, the therapeutic regimen is about 4.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 5.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 6.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 7.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 8.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 9.0 mg / kg / day. In some embodiments, the therapeutic regimen is about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0132] In some embodiments, the therapeutic regimen is administered orally. In some embodiments, the therapeutic regimen is administered parenterally. In some embodiments, the therapeutic regimen is administered intravenously.

[0133] In some embodiments, the subject is undergoing therapy with a compound that is converted to taurine chloramine in vivo in a human, for example a chlorite salt, for example, sodium chlorite. In some embodiments, the therapy is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 0.2 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 0.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 1.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 1.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 2.0 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the therapy is about 2.5 mg / kg / day to about 3.5 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0134] In some embodiments, the therapy is about 1.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapy is about 2.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapy is about 3.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapy is about 4.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the therapy is about 5.0 mg / kg / day to about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0135] In some embodiments, the therapy is about 0.2 mg / kg / day. In some embodiments, the therapy is about 0.5 mg / kg / day. In some embodiments, the therapy is about 1.0 mg / kg / day. In some embodiments, the therapy is about 1.2 mg / kg / day. In some embodiments, the therapy is about 1.4 mg / kg / day. In some embodiments, the therapy is about 1.6 mg / kg / day. In some embodiments, the therapy is about 1.8 mg / kg / day. In some embodiments, the therapy is aboutWSGR Docket No. 59077-714.6012.0 mg / kg / day. In some embodiments, the therapy is about 2.2 mg / kg / day. In some embodiments, the therapy is about 2.4 mg / kg / day. In some embodiments, the therapy is about 2.6 mg / kg / day. In some embodiments, the therapy is about 2.8 mg / kg / day. In some embodiments, the therapy is about 3.0 mg / kg / day. In some embodiments, the therapy is about 3.2 mg / kg / day. In some embodiments, the therapy is about 3.5 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0136] In some embodiments, the therapy is about 4.0 mg / kg / day. In some embodiments, the therapy is about 5.0 mg / kg / day. In some embodiments, the therapy is about 6.0 mg / kg / day. In some embodiments, the therapy is about 7.0 mg / kg / day. In some embodiments, the therapy is about 8.0 mg / kg / day. In some embodiments, the therapy is about 9.0 mg / kg / day. In some embodiments, the therapy is about 10.0 mg / kg / day. In some embodiments, the amount is based on subject body weight (or mass) of the compound based on mass of chlorite ion.

[0137] In some embodiments, the method further comprises administering to the subject therapy with a compound that is converted to taurine chloramine in vivo in a human, for example a chlorite salt, for example, sodium chlorite. In some embodiments, the method further comprises orally administering to the subject the therapy. In some embodiments, the method further comprisesparenterally administering to the subject the therapy. In some embodiments, the method further comprises intravenously administering to the subject the therapy.

[0138] A subject can be monitored for biomarkers for a condition prior to, during, or after receiving therapy for the neurodegenerative disease. For example, a subject who received, is receiving, or is recommended to receive sodium chlorite therapy for ALS can be monitored for biomarkers associated with the condition and the therapy.

[0139] Non-limiting examples of biomarkers relevant to the therapies herein include liposaccharide (LPS) and wound healing epidermal growth factor (EGF). Monitoring the levels of these biomarkers in a subject, for example, by HPLC analysis of blood draws, can provide information useful for therapeutic decisions. For example, a decision to begin therapy, continue therapy, or end therapy can be based on monitoring the levels of biomarkers in a subject, and by evaluating the ratio of the levels of the biomarkers in the subject over time. A decreasing ratio of LPS:EGF over time can be associated with successful therapy.

[0140] In some embodiments, the biomarker is transforming growth factor beta receptor 1 (TGFB1). In some embodiments, TGFB1 acts as a surrogate marker for alpha 2 macroglobulin (A2M) activation into a dimeric form. In some embodiments, the biomarker regulates the innate immune system.

[0141] FIG. 1 illustrates pathogenesis of ALS. FIG. 2 illustrates the same pathway whenWSGR Docket No. 59077-714.601 treated with Compound 1 (sodium chlorite). The figure indicates where EGF and LPS participate in the pathway.

[0142] Treatment of a subject who has a condition, for example, ALS, with a therapeutic ally- effective regimen herein can extend the term of the subject’s life. The term of life can be extended in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically - effective regimen. The term of life can be measured, for example, by periodic reporting to a supervising physician in person or via online portal. The term of life can be extended, for example, by about 1 month, about 2 months, about 3 months, about 4 months, about 4.8 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 0.5 years, about 1 year, about 1.5 years, about 2 years, about2.5 years, about 3 years, about 3.5 years, about 4 years, about 4.5 years, about 5 years, about 5.5 years, about 6 years, about 6.5 years, about 7 years, about 7.5 years, about 8 years, about 8.5 years, about 9 years, about 9.5 years, about 10 years, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 4.8 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 0.5 years, at least about 1 year, at least about 1.5 years, at least about 2 years, at least about 2.5 years, at least about 3 years, at least about 3.5 years, at least about 4 years, at least about 4.5 years, at least about 5 years, at least about 5.5 years, at least about 6 years, at least about 6.5 years, at least about 7 years, at least about 7.5 years, at least about 8 years, atleast about 8.5 years, at least about 9 years, at least about 9.5 years, at least about 10 years, at most about 1 month, at most about 2 months, at most about 3 months, at most about 4 months, at most about 4.8 months, at most about 5 months, at most about 6 months, at most about 7 months, at most about 8 months, at most about 9 months, at most about 10 months, at most about 11 months, at most about 12 months, at most about 0.5 years, at most about 1 year, at most about 1.5 years, at most about 2 years, at most about 2.5 years, at most about 3 years, at most about 3.5 years, at most about 4 years, at most about 4.5 years, at most about 5 years, at most about 5.5 years, at most about 6 years, at most about 6.5 years, at most about 7 years, at most about 7.5 years, at most about 8 years, at most about 8.5 years, at most about 9 years, at most about 9.5 years, or at most about 10 years.

[0143] Treatment of a subject who has a condition, for example, ALS, with a therapeutically - effective regimen herein can increase a subject’s survival probability. The survival probability can be in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effectiveWSGR Docket No. 59077-714.601 regimen. The survival probability can be increased, for example, by about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, about 0.1, about 0.11, about 0.12, about 0.13, about 0.14, about 0.15, about 0.16, about 0.17, about 0.18, about 0.19, about 0.2, about 0.21, about 0.22, about 0.23, about 0.24, about 0.25, about 0.26, about 0.27, about 0.28, about 0.29, about 0.3, at least about 0.01, at least about 0.02, at least about 0.03, at least about 0.04, at least about 0.05, at least about 0.06, at least about 0.07, atleast about 0.08, at least about 0.09, at least about 0.1, atleast about 0. il, at least about 0.12, at least about 0.13, at least about 0.14, at least about 0.15, at least about 0.16, at least about 0.17, atleast about 0.18, at least about 0.19, at least about 0.2, at least about 0.21, at least about 0.22, at least about 0.23, at least about 0.24, at least about 0.25, at least about 0.26, at least about 0.27, atleast about 0.28, at least about 0.29, at least about 0.3, at most about 0.01, at most about 0.02, at most about 0.03, at most about 0.04, at most about 0.05, at most about 0.06, at most about 0.07, at most about 0.08, at most about 0.09, at most about 0.1, at most about 0.11, at most about 0.12, at most about 0.13, at most about 0.14, at most about 0.15, at most about 0.16, at most about 0.17, at most about 0.18, at most about 0.19, at most about 0.2, at most about 0.21, at most about 0.22, at most about 0.23, at most about 0.24, at most about 0.25, at most about 0.26, at most about 0.27, at most about 0.28, at most about 0.29, or at most about 0.3.

[0144] Survival probability can be analyzed, for example, by Kaplan-Meier methodology. Kaplan-Meier methodology involves estimating conditional probabilities at each time point when an event occurs and taking the product limit of those probabilities to estimate the survival rate at each point in time. The values obtained can be expressed, for example, with a confidence interval. A confidence interval is a range of values that describes the uncertainty surrounding a reported value, such as a mean or median. A confidence interval can be identified, for example, by endpoints. A confidence interval can be, for example, 90%, 95%, or 99%. For example, patients treated with chlorite can have a 23% lower risk of death than placebo -treated patients over a 10-year period of follow-up. In patients up to 65 years old, an estimated 5-year survival rate can be about twice the rate in the placebo group (29% versus 15%).Compounds of the Disclosure

[0145] Disclosed herein are oxidative agents that can treat a condition with immune system dysregulation. In some embodiments, an oxidative agent of the disclosure can treat a condition with immune system dysregulation by inactivating macrophages. In some embodiments, the compound of the disclosure can be rapidly converted into a regulator of NFkB activation.

[0146] In some embodiments, the compound of the disclosure is chlorite (CIO2 ) or a pharmaceutically-acceptable salt thereof. In some embodiments, the compound of the disclosureWSGR Docket No. 59077-714.601 is sodium chlorite (NaC102). In some embodiments, the compound of the disclosure is potassium chlorite (KC102). In some embodiments, the compound is a pharmaceutically - acceptable ester of chlorous acid, for example, methyl chlorite or ethyl chlorite. In some embodiments, sodium chlorite can be converted from a prodrug to an intracellular form of taurine chloramine (TauCl) via a hyperchlorite intermediate. TauCl is a long-lived effector molecule within macrophages that down-regulatesNF-kB expression and inhibits production of pro-inflammatory cytokines in part through activation of heme oxygenase-1 (HO-1).

[0147] Any compound herein can be purified. A compound herein can be least 1% pure, at least 2% pure, at least 3% pure, at least 4% pure, at least 5% pure, at least 6% pure, at least 7% pure, at least 8% pure, at least 9% pure, at least 10% pure, at least 11% pure, at least 12% pure, at least 13% pure, at least 14% pure, at least 15% pure, at least 16% pure, at least 17% pure, at least 18% pure, at least 19% pure, at least 20% pure, at least 21% pure, at least 22% pure, at least 23% pure, at least 24% pure, at least 25% pure, at least 26% pure, at least 27% pure, at least 28% pure, at least 29% pure, at least 30% pure, at least 31% pure, at least 32% pure, at least 33% pure, at least 34% pure, at least 35% pure, at least 36% pure, at least 37% pure, at least 38% pure, at least 39% pure, at least 40% pure, at least 41% pure, at least 42% pure, at least 43% pure, at least 44% pure, at least 45% pure, at least 46% pure, at least 47% pure, at least 48% pure, at least 49% pure, at least 50% pure, at least 51% pure, at least 52% pure, at least 53% pure, at least 54% pure, at least 55% pure, at least 56% pure, at least 57% pure, at least 58% pure, at least 59% pure, at least 60% pure, at least 61% pure, at least 62% pure, at least 63% pure, at least 64% pure, at least 65% pure, at least 66% pure, at least 67% pure, at least 68% pure, at least 69% pure, at least 70% pure, at least 71% pure, at least 72% pure, at least 73% pure, at least 74% pure, at least 75% pure, at least 76% pure, at least 77% pure, at least 78% pure, at least 79% pure, at least 80% pure, at least 81% pure, at least 82% pure, at least 83% pure, at least 84% pure, at least 85% pure, at least 86% pure, at least 87% pure, at least 88% pure, at least 89% pure, at least 90% pure, at least 91% pure, at least 92% pure, at least 93% pure, at least 94% pure, at least 95% pure, at least 96% pure, at least 97% pure, at least 98% pure, at least 99% pure, at least 99.1% pure, at least 99.2% pure, at least 99.3% pure, at least 99.4% pure, at least 99.5% pure, at least 99.6% pure, at least 99.7% pure, at least 99.8% pure, or at least 99.9% pure. In some embodiments, a compound of the disclosure can be at least about 90% pure. In some embodiments, a compound of the disclosure can be at least about 95% pure. In some embodiments, a compound of the disclosure can be at least about 98% pure. In some embodiments, a compound of the disclosure can be at least about 99% pure. In some embodiments, a compound of the disclosure can be at least about 99.5% pure. In some embodiments, a compound of the disclosure can be at least about 99.8% pure.WSGR Docket No. 59077-714.601Chlorite Compositions

[0148] In some embodiments, the active agent described herein is an aqueous pharmaceutical formulation. In some embodiments, the aqueous pharmaceutical formulation comprises sodium chlorite and a saline solution.

[0149] In various embodiments, the pH of the aqueous pharmaceutical formulation is about 7 to about 11 . In some embodiments, the pH of the aqueous pharmaceutical formulation is about 7 to about 9.5. In some embodiments, the aqueous pharmaceutical formulation includes a buffer. Non-limiting examples of buffers include phosphate buffers, borate buffers, citrate buffers, and carbonate buffers. In some embodiments, the buffer is a phosphate buffer such as monosodium phosphate or disodium phosphate. In some embodiments, any of the formulations or pharmaceutical formulations described herein comprises a pH adjusting agent that consists essentially of a phosphate salt or a mixture of phosphate salts.

[0150] In some embodiments, the pH of a chlorite formulation for use with the present disclosure can be adjusted to between about 7 and about 11.5. In some embodiments, the pH of a chlorite formulation is lowered to between about 7 and about 11.5 using a pH adjusting compound that does not expose the formulation to high local acidity. In some embodiments, the pH adjusting compound is any one or more of monosodium phosphate, disodium phosphate, or acetic acid.

[0151] In some embodiments, the pH adjusting agent(s) or pH adjusting compound(s) are weak acids or weak bases having a pKa of about 4 to about 9, a pKa of about 5 to about 9, or a pKa of about 5 to about 8, or a pKa of about 6 to about 7.5. Examples include but are not limited to a phosphate buffer having a pKa of about 4 to about 9, for example, monobasic phosphates, or monosodium phosphate and / or disodium phosphate and lower alkanoic acids, for example, acetic acid or propionic acid. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7 and about 11.5 using a pH adjusting compound that does not expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7 and about 10 using a pH adjusting compound that doesnot expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7 and about 9.5 using a pH adjusting compound that does not expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7 and about 9.0 using a pH adjusting compound that doesWSGR Docket No. 59077-714.601 not expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7 and about 8.5 using a pH adjusting compound that does not expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound. In some embodiments, the pH of a formulation sensitive to acidity is lowered to between about 7.1 and about 7.7 using a pH adjusting compound that does not expose the formulation to acidity, including but not limited to a high local acidity in the area around the pH adjusting compound.

[0152] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated, for example, using suitable dispersing or wetting agents and suspending agents. An injectable preparation can be a sterile, injectable solution, suspension, or emulsion in a nontoxic, parenterally-acceptable diluent or solvent, for example, as a solution in 1,3 -butanediol. Non-limiting examples of suitable vehicles and solvents include Water for Injection (WFI, USP), Sterile Water for Injection (SWFI, USP), Ringer’s solution, USP, and isotonic solution, such as isotonic sodium chloride solution. In some embodiments, a sterile, fixed oil is used as a solvent or suspending medium. In some embodiments, a fatty acid such as oleic acid is formulated in an injectable.

[0153] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In some embodiments, the injectable formulations are sterile, pyrogen free, and free of particulates according to USP -NF standards. In some embodiments, sterility, pyrogenicity, and particulates assays are conducted according to USP-NF protocols.

[0154] In some embodiments, the pharmaceutically acceptable chlorite salt is administered in an amount ranging from 0.1 to 10 mg / kgbody mass. In some embodiments, the chlorite salt is administered more than once in a month, such as at least once per week for a period of at least one month. In some embodiments, the chlorite salt is administered for at least a year.

[0155] In some embodiments, the chlorite formulations for use with the present invention comprise low amounts of chlorate ion, sulfate ion, or chloride ion. In some embodiments, the composition is substantially free of sulfate ion.

[0156] In some embodiments, a formulation herein contains an amount of chloride ions than is less than about 1 .9% of the chlorite ions by mass in the formulation, for example, less than about 1.8%; less than about 1.5%; less than about 1.0%; less than about 0.5%; less than about 0.3%; less than about 0.1%; less than about 0.05%; less than about 0.01%; less than about 0.001%; from about 0.001 to about 0.1%; from about 0.1 to about 0.5%; from about 0.5 to about 1.0%;WSGR Docket No. 59077-714.601 from about 1.0 to about 1.5%; or from about 1.5 to about 1.8%.

[0157] In some embodiments, a formulation herein contains less than an amount of chlorate ions that is less than about 1.5% of chlorate ions by mass in the formulation, for example, less than about 1.4%, less than about 1.3%; less than about 1.0%; less than about 0.5%; less than about 0.3%; less than about 0.1%; less than about 0.01%; less than about 0.001%; from about 0.001 to about 0.1%; from about 0.001 to about 0.01%; from about 0.01 to about 0.1%; from about 0.1 to about 0.5%; from about 0.5 to about 1.0%; or from about 1.0 to about 1.4% of chlorate ions. In some embodiments, a formulation herein is substantially free of chlorate ions. In some embodiments, a formulation herein contains less than about 0.5% of chlorate ions by mass in the formulation. In some embodiments, a formulation herein contains less than about 0.19% of chlorate ions by mass in the formulation. In some embodiments, a formulation herein contains less than about 0.1% of chlorate ions by mass in the formulation. In some embodiments, the level of chlorate ions is below the level of detection using HPLC.

[0158] In some embodiments, a formulation herein contains less than an amount of sulfate ions that is less than about 0.7% of sulfate ions by mass in the formulation, for example, less than about 0.65%, less than about 0.6%; less than about 0.5%; less than about 0.4%; less than about 0.3%; less than about 0.2%; less than about 0.1%; less than about 0.08%; less than about 0.07%; less than about 0.06%; less than about 0.05%; less than about 0.005%; less than about 0.0005%; from about 0.001 to about 0. 1%; from about 0.01 to about 1%; from about O.Ol to about 0.5%; from about 0.06 to about 0.08%; or from about 0.5 to about 0.65%. In some embodiments, a formulation herein is substantially free of sulfate ions. In some embodiments, a formulation herein contains less than about 0.5% of sulfate ions by mass in the formulation. In some embodiments, a formulation herein contains less than about 0.08% of sulfate ions by mass in the formulation. In some embodiments, the level of sulfate ions is below the level of detection using HPLC.

[0159] In some embodiments, a formulation herein contains less than an amount of chloride ions that is less than about 0.5% of chloride ions by mass in the formulation, for example, less than about 0.24%, less than about 0.2%; or less than about 0.1%. In some embodiments, a formulation herein contains less than about 0.2% of chloride ions by mass in the formulation. In some embodiments, a formulation herein contains less than about 0. 1% of chloride ions by mass in the formulation. In some embodiments, the level of chloride ions is below the level of detection using HPLC.

[0160] In some embodiments, the chlorite formulations described herein comprise no greater than about 10% by weight of by-products or impurities present in commercially available, technical grade chlorite. Non-limiting examples of by-products or impurities present inWSGR Docket No. 59077-714.601 commercially available, technical grade chlorite include chlorate ion, sulfate ion, chlorine dioxide, chloride ion, sodium bicarbonate, and sodium carbonate. In some embodiments, the chlorite formulations described herein comprise no greater than about any of about 15%, about 12%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, ab out 2% , ab out 1 % , ab out 0.5 %, ab out 0.3 %, ab out 0.1 %, f rom ab out 0.1% to ab out 5 % ; f rom about 5% to about 10%; or from about 10% to about 15% by mass of one or more degradation products or impurities present in commercially available, technical grade sodium chlorite. In some embodiments, the chlorite formulations described herein comprise no greater than about 0.5% by mass of degradation products or impurities present in commercially available, technical grade sodium chlorite. In some embodiments, the chlorite formulations described herein comprise no greater than about 5% by mass of degradation products or impurities present in commercially available, technical grade sodium chlorite. In some embodiments, the sodium chlorite formulations described herein are substantially free of the degradation products or impurities present in commercially available, technical grade sodium chlorite.

[0161] In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite. In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than 2.0% sodium chloride, wherein the purified sodium chlorite comprises no more than 1.0% sodium chlorate, and wherein the chlorite composition comprises dibasic sodium phosphate and has a pH between 7.5 and 9.5.

[0162] In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than about 1.0% sodium chloride, wherein the purified sodium chlorite comprises no more than about 1.0% sodium chlorate, and wherein the chlorite composition comprises a buffer and has a pH from about 7 to about 8. In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than about 0.8% sodium chloride, wherein the purified sodium chlorite comprises no more than about 0.8% sodium chlorate, and wherein the chlorite composition comprises a buffer and has a pH from about 7 to about 8. In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than about 0.6% sodium chloride, wherein the purified sodium chlorite comprises no more than about 0.6% sodium chlorate, and wherein the chlorite composition comprises a buffer and has a pH from about 7 to about 8. In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than about 0.5% sodium chloride, wherein the purified sodium chlorite comprises no more than about 0.5%WSGR Docket No. 59077-714.601 sodium chlorate, and wherein the chlorite composition comprises a buffer and has a pH from about ? to about 8. In some embodiments, the chlorite formulations described herein comprise purified sodium chlorite, wherein the purified sodium chlorite comprises no more than about 0.5% sodium chloride, wherein the purified sodium chlorite comprises no more than about 0.5% sodium chlorate, and wherein the chlorite composition comprises a buffer and has a pH from about 7.5 to about 7.7.

[0163] Administration can be, for example, by infusion. Infusion can occur over an infusion time of, for example, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. Infusion can be at an infusion site, for example, in the arm, leg, back, or any other suitable body part. If the subject experiences an adverse reaction such as pain, redness, swelling, or discomfort at the infusion site, then the infusion can be extended, for example, from about 30 minutes to about 60 minutes.

[0164] A regimen herein can last as long as is needed to be effective, for example, until the subject dies. A regimen herein can last, for example, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 1 year, about 1.25 years, about 1.5 years, about 1.75 years, about 2 years, about 2.25 years, about 2.5 years, about 2.75 years, about 3 years, about 3.25 years, about 3.5 years, about 3.75 years, about 4 years, about 4.25 years, about 4.5 years, about 4.75 years, about 5 years, about 5.25 years, about 5.5 years, about 5.75 years, about 6 years, about 6.25 years, about 6.5 years, about 6.75 years, about ? years, about 7.25 years, about 7.5 years, about 7.75 years, about 8 years, about 8.25 years, about 8.5 years, about 8.75 years, about 9 years, about 9.25 years, about 9.5 years, about 9.75 years, about 10 years, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 1 year, at least about 1.25 years, at least about 1.5 years, at least about 1.75 years, at least about 2 years, at least about 2.25 years, at least about 2.5 years, at least about 2.75 years, at least about 3 years, at least about 3.25 years, at least about 3.5 years, at least about 3.75 years, at least about 4 years, at least about 4.25 years, atleast about4.5 years, at least about4.75 years, at least about 5 years, at least about 5.25 years, atleast about 5.5 years, at least about 5.75 years, at least about 6 years, at least about 6.25 years, at least about 6.5 years, at least about 6.75 years, at least about 7 years, at least about 7.25 years, at least about 7.5 years, at least about 7.75 years, atleast about 8 years, at least about 8.25 years, atleast about 8.5 years, at least about 8.75 years, at least about 9 years, at least about 9.25 years, at least about 9.5 years, at least about 9.75 years, atleast about 10 years at most about 6 months, at most about ? months, at most about 8 months, at most about 9 months, at most about 10 months, at most about 11 months, atWSGR Docket No. 59077-714.601 most about 12 months, at most about 1 year, at most about 1.25 years, at most about 1.5 years, at most about 1.75 years, at most about 2 years, at most about 2.25 years, at most about 2.5 years, at most about 2.75 years, at most about 3 years, at most about 3.25 years, at most about 3.5 years, at most about 3.75 years, at most about 4 years, at most about 4.25 years, at most about 4.5 years, at most about 4.75 years, at most about 5 years, at most about 5.25 years, at most about 5.5 years, at most about 5.75 years, at most about 6 years, at most about 6.25 years, at most about 6.5 years, atmost about 6.75 years, at most about 7 years, at most about 7.25 years, at most about 7.5 years, at most about 7.75 years, at most about 8 years, at most about 8.25 years, at most about 8.5 years, at most about 8.75 years, at most about 9 years, at most about 9.25 years, at most about 9.5 years, at most about 9.75 years, or at most about 10 years.

[0165] After some portion of the regimen has ended, for example, six months, a subject can be assessed for wellbeing in light of the condition being treated, for example, ALS. The assessment can be, for example, a vital capacity test. Vital capacity is the greatest volume of air that can be expelled from the lungs after taking the deepest possible breath . As ALS progresses, patients lose the ability to breathe without assistance as the motor neurons controlling the diagraph succumb to the disease, eventually resulting in tracheotomy and institution of a ventilator to prolong patient life.

[0166] Reduction in vital capacity can be used to measure ALS disease progression, including percent change from baseline vital capacity. Vital capacity can be about 4800 mL and varies by age and body size. Vital capacity can be calculated by summing tidal volume, inspiratory reserve volume, and expiratory reserve volume. VC = TV+IRV+ERV. Vital capacity for a given patient can be measured using, for example, a spirometer (spirometry). Measuring vital capacity can be useful for assessing ALS disease progression for a given patient.

[0167] Vital capacity can be, for example, measured or predicated. Measured vital capacity is the value that is determined experimentally. Predicated vital capacity is a calculation based on factors such as age, gender and height.

[0168] Vital capacity can be, for example, forced vital capacity. Forced vital capacity is the maximum amount of air that a person can exhale after inhaling as deeply as possible. Forced vital capacity is measured by a spirometry test. To measure forced vital capacity, a subject is seated and instructed to breathe comfortably. A clip is placed over the subject 's nose. The subject is given a tube into which to breathe. The subject is instructed to inhale as deeply as possible. The subject is instructed to exhale as forcefully as possible into the tube.

[0169] Vital capacity can be, for example, slow vital capacity. Slow vital capacity is a measure of lung function that tests how much air a person can exhale slowly and steadily after taking a deep breath. To measure slow vital capacity, the subject sits comfortably and clips a nose clip toWSGR Docket No. 59077-714.601 the nose. The subject takes a deep breath, holds for a few seconds, then slowly and steadily exhales as much air as possible over about 15 seconds. The amount of air exhaled is recorded.

[0170] An amount of vital capacity can be lost as a result of ALS. Loss can be represented as a percentage loss of vital capacity. The percent loss can be, for example, relative to a reference or absolute, a loss of vital capacity can be, for example, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at most about 5%, at most about 10%, at most about 15%, at most about 20%, at most about 25%, or at most about 30%.

[0171] The regimen of administration can involve administration in an amount and at a frequency to provide a desired effect. For example, chlorite or a chlorite -containing agent can be administered for 2, 3, 4, 5, 6, 7, 8, 9, 10, or more consecutive days. Administration can be daily, for example, once a day. In some embodiments, sodium chlorite is administered daily. Administration can occur, for example, by an initial treatment cycle with daily dosing for 5 days, followed by a 23 -day drug-free period, then subsequent treatment cycles with daily dosing for 3 days, followed by 25-day drug-free periods. Administration can occur, for example, by an initial treatment cycle with daily dosing for 5 days of a month, then sub sequent treatment cycles with daily dosing for 3 days of a month.

[0172] In some embodiments, the pharmaceutical composition can be administered in a cycle. A non-limiting example of a cycle provides: a) a first period of time wherein the pharmaceutical composition is administered at a first dose for a first number of times; andb) a second period of time wherein the pharmaceutical composition is administered at a second dose for a second number of times. In some embodiments, the cycle is performed about 2-4 times.

[0173] In some embodiments, the dosing schedule provides periods of administration alternating with periods of non-administration. In some embodiments, sodium chlorite is administered in a four-week cycle. In some embodiments, sodium chlorite is administered in a three-week cycle. In some embodiments, the cycle could be repeated as necessary to achieve the desired result. In some embodiments, sodium chlorite is administered in a two-week cycle. In some embodiments, a total of 2-4 cycles are performed. In some embodiments, a total of about 4 cycles, about 5 cycles, about 6 cycles, about 7 cycles, about 8 cycles, about 9 cycles, about 10 cycles, about 11 cycles, about 12 cycles, about 13 cycles, or about 14 cycles are performed. In some embodiments, a total of about 6 cycles are performed. In some embodiments, a total of about 10 cycles are performed. In some embodiments, a total of about 12 cycles are performed.

[0174] In some embodiments, the chlorite formulation described herein is administered daily for a first number of days in a row in a first month and administered daily for a second number of days in subsequent months. In some embodiments, the first number of days is about 2, aboutWSGR Docket No. 59077-714.6013, about 4, about 5, about 6, or about 7. In some embodiments, the first number of days is about 2. In some embodiments, the first number of days is about 3. In some embodiments, the first number of days is about 4. In some embodiments, the first number of days is about 5. In some embodiments, the first number of days is about 6. In some embodiments, the first number of days is about 7. In some embodiments, the second number of days is about 2. In some embodiments, the second number of days is about 3. In some embodiments, the second number of days is about 4. In some embodiments, the second number of days is about 5. In some embodiments, the second number of days is about 6. In some embodiments, the second number of days is about 7.

[0175] In some embodiments, the chlorite formulation described herein is initially administered daily for 5 days in a row in the first month, and daily for 3 days in a row in subsequent months . In some embodiments, the chlorite formulation described herein is initially administered daily for 5 days in a row in the first month, and daily for 3 days in a row in subsequent months, wherein the chlorite formulation comprises purified sodium chlorite, wherein the purified sodium chlorite is at least 97% pure, wherein the purified sodium chlorite comprises no more than 2% sodium chloride, wherein the purified sodium chlorite comprises no more than 1% sodium chlorate, and wherein the chlorite composition comprises dibasic sodium phosphate and has a pH from about 7.5 to about 9.5. In some embodiments, the chlorite formulation described herein is initially administered daily for 5 days in a row in the first month, and daily for 3 days in a row in subsequent months, wherein the chlorite formulation comprises purified sodium chlorite, wherein the purified sodium chlorite is at least 97% pure, wherein the purified sodium chlorite comprises no more than 2% sodium chloride, wherein the purified sodium chlorite comprises no more than 1% sodium chlorate, and wherein the chlorite composition comprises dibasic sodium phosphate andhas a pH from about 7.5 to about 8.5. In some embodiments, the chlorite formulation described herein is initially administered daily for 5 days in a row in the first month, and daily for 3 days in a row in sub sequent months, wherein the chlorite formulation comprises purified sodium chlorite, wherein the purified sodium chlorite is at least 97% pure, wherein the purified sodium chlorite comprises no more than 2% sodium chloride, wherein the purified sodium chlorite comprises no more than 1% sodium chlorate, and wherein the chlorite composition comprises dibasic sodium phosphate and has a pH from about 7.5 to about 8.

[0176] In some embodiments, the administrations of the chlorite salt occur about every other day of the regimen. In some embodiments, the administrations of the chlorite salt occur about every day of the regimen.

[0177] In some embodiments, the subject received another treatment for the condition, for example, ALS, prior to receiving a treatment described herein. In some embodiments, theWSGR Docket No. 59077-714.601 subject received riluzole for the condition, for example, ALS, prior to receiving a treatment described herein. In some embodiments, the subject responded to therapy with riluzole. In some embodiments, the subject did not respond to therapy with riluzole. In some embodiments, the subject is refractory to treatment with riluzole.

[0178] Any compositions and pharmaceutical formulation described herein can be used in kits. In some embodiments, the kits are intended for administration of sodium chlorite or a sodium chlorite-containing agent, or pharmaceutical formulations comprising such agents. The kits can include a unit dosage amount of the agents or formulations as described herein. In some variations, the kits comprise suitable packaging. In some embodiments, the kits comprise instructions for use of the active agent in a neurodegenerative disease as described above. In some embodiments, the kit contains instructions for using sodium chlorite formulations to treat a neurodegenerative disease as described herein. In some embodiments, a kit contains suitable instructions for practicing any of the treatment methods described herein with a formulation described herein. In some embodiments, a kit is used to treat any one or more of the diseases or conditions described herein. A kit can comprise an aid to administration of the active agent formulation, such as a syringe for injection or pressure pack for oral forms.Pharmaceutical Compositions

[0179] A pharmaceutical composition of the invention can be a combination of any compounds described herein with other chemical components, such as carriers, stabilizers, solubilizers, tonicity enhancing agents, buffers, preservatives, diluents, dispersing agents, suspending agents, thickening agents, and / or excipients. The pharmaceutical compositions can include at least one pharmaceutically -acceptable carrier, stabilizer, solubilizer, tonicity enhancing agent, buffer, preservative, diluent, dispersing agent, suspending agent, thickening agent, and / or excipients and a compound described herein, for example, pharmaceutically-acceptable salt form. The pharmaceutical composition facilitates administration of the compound to an organism. Pharmaceutical compositions can be administered in therapeutically -effective amounts as pharmaceutical compositions by various forms and routes including, for example, intravenous, subcutaneous, intramuscular, oral, parenteral, ophthalmic, subcutaneous, transdermal, nasal, vaginal, and topical administration. Pharmaceutical compositions can be formulated using one or more physiologically-acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations that can be used pharmaceutically. Formulations can be modified depending upon the route of administration chosen.

[0180] A pharmaceutical composition can be administered in a local manner, for example, via injection of the compound directly into an organ, optionally in a depot or sustained releaseWSGR Docket No. 59077-714.601 formulation or implant. Pharmaceutical compositions can be provided in the form of a rapid release formulation, in the form of an extended release formulation, or in the form of an intermediate release formulation. A rapid release form can provide an immediate release. An extended release formulation can provide a controlled release or a sustained delayed release.

[0181] In some embodiments, a pharmaceutical composition can be formulated for oral administration. In some embodiments, a pharmaceutical composition formulated for oral administration can be formulated by combining one or more compounds of the disclosure with one or more pharmaceutically -acceptable carriers or excipients. Such carriers can be used to formulate liquids, gels, syrups, elixirs, slurries, or suspensions, for oral ingestion by a subject. Non-limiting examples of solvents used in an oral dissolvable formulation can include water, ethanol, isopropanol, saline, physiological saline, DMSO, dimethylformamide, potassium phosphate buffer, phosphate buffer saline (PBS), sodium phosphate buffer, 4 -2-hydroxy ethyl- 1- piperazineethanesulfonic acid buffer (HEPES), 3-(N-morpholino)propanesulfonic acid buffer (MOPS), piperazine-N,N'-bis(2-ethanesulfonic acid) buffer (PIPES), and saline sodium citrate buffer (SSC). Non-limiting examples of co-solvents used in an oral dissolvable formulation can include sucrose, urea, cremaphor, DMSO, and potassium phosphate buffer.

[0182] In some embodiments, a pharmaceutical composition can be formulated for intravenous administration. The pharmaceutical compositions can be in a form suitable for parenteral injection as a sterile suspension, solution, or emulsion in oily or aqueous vehicles, and can contain formulation agents such as suspending, stabilizing and / or dispersing agents.Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Suspensions of the active compounds can be prepared as oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. The suspension can also contain suitable stabilizers or agents that increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient can be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0183] In some embodiments, a pharmaceutical composition can be formulated for topical administration. In some embodiments, a pharmaceutical composition can be formulated into a variety of topically administrable compositions, such as solutions, suspensions, lotions, gels, pastes, medicated sticks, balms, creams, and ointments. Such pharmaceutical compositions can contain solubilizers, stabilizers, tonicity enhancing agents, buffers, and preservatives. In some embodiments, a pharmaceutical composition of the disclosure can be applied topically to the skin, or a body cavity, for example, oral, vaginal, bladder, cranial, spinal, thoracic, or pelvicWSGR Docket No. 59077-714.601 cavity of a subject. In some embodiments, a compound or pharmaceutical composition of the disclosure can be applied to an accessible body cavity.

[0184] In practicing the methods of treatment or use provided herein, therapeutically -effective amounts of the compounds described herein are administered in pharmaceutical compositions to a subject having a disease or condition to be treated. A therapeutically -effective amount can vary widely depending on the severity of the disease, the age and relative health of the subject, the potency of the compounds used, and other factors. The compounds can be used singly or in combination with one or more therapeutic agents as components of mixtures.

[0185] Pharmaceutical compositions comprising a compound described herein can be manufactured, for example, by mixing, dissolving, emulsifying, encapsulating, entrapping, or compression processes. Methods for the preparation of compositions comprising the compounds described herein include formulating the compounds with one or more inert, pharmaceutically - acceptable excipients or carriers to form a solid, semi-solid, or liquid composition. Solid compositions include, for example, powders, tablets, dispersible granules, capsules, and cachets. Liquid compositions include, for example, solutions in which a compound is dissolved, emulsions comprising a compound, or a solution containing liposomes, micelles, or nanoparticles comprising a compound as disclosed herein. Semi-solid compositions include, for example, gels, suspensions and creams. The compositions can be in liquid solutions or suspensions, solid forms suitable for solution or suspension in a liquid prior to use, or as emulsions. These compositions can also contain minor amounts of nontoxic, auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, and other pharmaceutically -acceptable additives.

[0186] Non-limiting examples of dosage forms suitable for use in the invention include liquid, powder, gel, nanosuspension, nanoparticle, microgel, aqueous or oily suspensions, emulsion, elixir, nanosuspension, aqueous or oily suspensions, drops, syrups, and any combination thereof.

[0187] Non-limiting examples of pharmaceutically -acceptable excipients suitable for use include binding agents, disintegrating agents, anti -adherents, anti-static agents, surfactants, antioxidants, coating agents, coloring agents, plasticizers, preservatives, suspending agents, emulsifying agents, anti -microbial agents, spheronization agents, granulating agents, lubricating agents, sweetening agents, glidants, gums, flavoring agents, plant cellulosic material, and any combination thereof.

[0188] A pharmaceutical composition of the invention can be, for example, an immediate release form or a controlled release formulation. An immediate release formulation can be formulated to allow the compounds to act rapidly. Non-limiting examples of immediate release formulations include readily dissolvable formulations. A controlled release formulation can be aWSGR Docket No. 59077-714.601 pharmaceutical formulation that has been adapted such that release rates and release profiles of the active agent can be matched to physiological and chronotherapeutic requirements or, alternatively, has been formulated to effect release of an active agent at a programmed rate. Non-limiting examples of controlled release formulations include granules, delayed release granules, hydrogels (e.g., of synthetic or natural origin), other gelling agents (e.g., gel-forming dietary fibers), matrix -based formulations (e.g., formulations comprising a polymeric material having at least one active ingredient dispersed through), granules within a matrix, polymeric mixtures, and granular masses.

[0189] In some embodiments, a controlled release formulation is a delayed release formulation. A delayed release formulation can be formulated to delay a compound’s action for an extended period of time. A delayed release form can be formulated to delay the release of an effective dose of one or more compounds, for example, for about 4, about 8, about 12, about 16, or about 24 hours.

[0190] In some embodiments, a controlled release formulation can be a sustained release formulation. A sustained release formulation can be formulated to sustain, for example, the compound’s action over an extended period of time. A sustained release form can be formulated to provide an effective dose of any compound described herein (e.g., provide a physiologically - effective blood profile) over about 4, about 8, about 12, about 16 or about 24 hours.

[0191] Non-limiting examples of pharmaceutically -acceptable excipients can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and DrugDelivery Systems, Seventh Ed. (Lippincott Williams & Wilkinsl999), each of which is incorporated by reference in its entirety.

[0192] Depending on the intended mode of administration, the pharmaceutical compositions can be in the form of solid, semi-solid or liquid dosage forms, such as, for example, tablets, suppositories, pills, capsules, powders, liquids, suspensions, lotions, creams, or gels, for example, in unit dosage form suitable for single administration of a precise dosage.

[0193] For solid compositions, nontoxic solid carriers include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose, glucose, sucrose, and magnesium carbonate.

[0194] Pharmaceutical compositions described herein can be in unit dosage forms suitable for single administration of precise dosages. In unit dosage form, the formulation is divided into unit doses containing appropriate quantities of one or more compounds. The unit dosage can beWSGR Docket No. 59077-714.601 in the form of a package containing discrete quantities of the formulation. Non -limiting examples are packaged injectables, vials, or ampoules. Aqueous suspension compositions can be packaged in single-dose non-reclosable containers. Multiple-dose reclosable containers can be used, for example, in combination with or without a preservative. Formulations for injection can be presented in unit dosage form, for example, in ampoules, or in multi -dose containers with a preservative. Non-limiting examples of a preservative include benzalkonium, benzyl benzoate, propylparaben, parabens, benzyl alcohol, chlorobutanol, benzoic acid, potassium sorbate, phenol, ethyl alcohol, and methylparaben.

[0195] A pharmaceutical composition can have a pH adjusted to from about 7 and to about11.5. In some embodiments, the pH of a pharmaceutical composition of the disclosure can be adjusted using an agent that does not expose the formulation to high local acidity. In some embodiments, the pH of a pharmaceutical composition of the disclosure can be adjusted using, for example, monosodium phosphate, disodium phosphate, dibasic sodium phosphate, or acetic acid.

[0196] In some embodiments, a pharmaceutical composition of the disclosure can have a pH of from about ? to about 7.5, from about 7.5 to about 8, from about 8 to about 8.5, from about 8.5 to about 9, from about 9 to about 9.5, from about 9.5 to about 10, from about 10 to about 10.5, from about 10.5 to about 11, from about 11 to about 11.5, or from about 11.5 to about 12. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of from about 7 to about 7.5. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of from about 7.5 to about 8. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of from about 8 to about 8.5. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of from about 7.5 to about 9.5.

[0197] In some embodiments, a pharmaceutical composition of the disclosure can have a pH of less than about 12. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of less than about 11.5, less than about 11, less than about 10.5, less than about 10, less than about 9.5, less than about 9, less than about 8.5, less than about 8, less than about 7.5, less than about ?, less than about 6.5, or less than about 6. In some embodiments, the pH of a pharmaceutical composition of the disclosure can have a pH of less than about 11.5. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of less than about10.5. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of less than about 8.5. In some embodiments, a pharmaceutical composition of the disclosure can have a pH of less than about 7.5. In some embodiments, a pharmaceutical composition of the disclosure has a pH of about 7.4. In some embodiments, a pharmaceutical composition of the disclosure has a pH that is at a physiological level.WSGR Docket No. 59077-714.601

[0198] In some embodiments, a pharmaceutical composition of the disclosure can comprise a solvent. In some embodiments, a pharmaceutical composition of the disclosure can comprise water as a solvent. In some embodiments, a pharmaceutical composition of the disclosure is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is at least about 80% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is at least about a 90% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is at least about a 95% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is at least about a 98% (v / v) water.

[0199] In some embodiments, a pharmaceutical composition of the disclosure is from about 50% to about 60%, from about 60% to about 70%, from about 70% to about 80%, from about 80% to about 90%, or from about 90% to about 98% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is from about 80% to about 90% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is from about 90% to about 95% (v / v) water. In some embodiments, a pharmaceutical composition of the disclosure is from about 90% to about 98% (v / v) water.

[0200] In some embodiments, a pharmaceutical composition comprises from about 1 pM to about 1.5 M of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 1 pM to about 10 pM, from about 10 pM to about 50 pM, from about 50 pMto about 100 pM, from about 0. 1 mM to about 0.5 mM, from about 0.5 mM to about 1 mM, from about 1 mMto about 25 mM, from about 25 mM to about 100 mM, from about 100 mMto about 250 mM, from about 250 mMto about 500 mM, from about 500 mM to about 750 mM, or from about 750 mMto about 1000 mM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 1 pM to about 10 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 10 pM to about 50 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 50 pMto about 100 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 100 pMto about 250 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 250 pMto about 500 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises from about 1 mM to about 5 mM of a compound of the disclosure.

[0201] In some embodiments, a pharmaceutical composition comprises at least about 1 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprisesWSGR Docket No. 59077-714.601 at least about 1 pM, atleast about 10 pM, at least about 50 pM, at least about 100 pM, at least about 250 pM, at least about 500 pM, at least about 750 pM, at least about 1 mM, at least about 25 mM, at least about 50 mM, at least about 75 mM, at least about 100 mM, at least about 250 mM, at least about 500 mM, at least about 750 mM, or at least about 1000 mM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 1 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 10 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises atleast about 25 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 50 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 60 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 65 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 100 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 250 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises at least about 500 pM of a compound of the disclosure.

[0202] In some embodiments, a pharmaceutical composition comprises about 1 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 1 pM, about 10 pM, about 50 pM, about 100 pM, about 250 pM, about 500 pM, about 750 pM, about 1 mM, about 25 mM, about 50 mM, about 75 mM, about 100 mM, about 250 mM, about 500 mM, about 750 mM, or about 1000 mM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 1 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 10 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 25 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 50 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 100 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 250 pM of a compound of the disclosure. In some embodiments, a pharmaceutical composition comprises about 500 pM of a compound of the disclosure.

[0203] In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 0.5 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 0.5 mg / mL, at least about 1 mg / mL, at least about 1.5 mg / mL, at least about 2 mg / mL, at least about 2.5 mg / mL, at least about 3 mg / mL, at least about 3.5 mg / mL, at least about 4 mg / mL, at least about 4.5 mg / mL, at leastWSGR Docket No. 59077-714.601 about 5 mg / mL, at least about 5.5 mg / mL, at least about 6 mg / mL, at least about 6.5 mg / mL, at least about 7 mg / mL, at least about 7.5 mg / mL, at least about 8 mg / mL, at least about 8.5 mg / mL, at least about 9 mg / mL, at least about 9.5 mg / mL, or at least about 10 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 2 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 4 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 5 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 5.6 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 5.5 mg / mL of sodium chlorite. In some embodiments, a pharmaceutical composition of the disclosure comprises at least about 4 mg / mL of chlorite.

[0204] In some embodiments, a pharmaceutical composition of the disclosure comprises from about 0.5 mg / mL to about 10 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises from about 0.5 mg / mL to about 1 mg / mL, from about 1 mg / mL to about 2 mg / mL, from about 2 mg / mL to about 3 mg / mL, from about 3 mg / mL to about 4 mg / mL, from about 4 mg / mL to about 5 mg / mL, from about 5 mg / mL to about 6 mg / mL, from about 6 mg / mL to about 7 mg / mL, from about 7 mg / mL to about 8 mg / mL, from about 8 mg / mL to about 9 mg / mL, or from about 9 mg / mL to about 10 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises from about 4 mg / mL to about 5 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises from about 5 mg / mL to about 6 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises from about 4 mg / mL to about 5 mg / mL of chlorite. In some embodiments, a pharmaceutical composition of the disclosure comprises from about 5 mg / mL to about 6 mg / mL of sodium chlorite.

[0205] In some embodiments, a pharmaceutical composition of the disclosure comprises about 0.5 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 0.5 mg / mL, about 1 mg / mL, about 1.5 mg / mL, about 2 mg / mL, about 2.5 mg / mL, about 3 mg / mL, about 3.5 mg / mL, about 4 mg / mL, about 4.5 mg / mL, about 5 mg / mL, about 5.5 mg / mL, about 6 mg / mL, about 6.5 mg / mL, about 7 mg / mL, about 7.5 mg / mL, about 8 mg / mL, about 8.5 mg / mL, about 9 mg / mL, about 9.5 mg / mL, or about 10 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 2 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 4 mg / mLWSGR Docket No. 59077-714.601 of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 5 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 5.6 mg / mL of a compound of the disclosure. In some embodiments, a pharmaceutical composition of the disclosure comprises about 5.5 mg / mL of sodium chlorite. In some embodiments, a pharmaceutical composition of the disclosure comprises about 4 mg / mL of chlorite.

[0206] In some embodiments, a pharmaceutical composition of the disclosure is formulated for intravenous administration. In some embodiments, a pharmaceutical composition of the disclosure comprises dibasic sodium phosphate. In some embodiments, a pharmaceutical composition of the disclosure has a pH of from about 7.5 to about 9.5. In some embodiments, the pharmaceutical composition of the disclosure does not comprise any preservatives. In some embodiments, the pharmaceutical composition of the disclosure comprises about 4 mg / mL of chlorite. In some embodiments, the pharmaceutical composition of the disclosure comprises about 5.5 mg / mL of sodium chlorite.Subject Selection

[0207] In some embodiments, the disclosure provides a method comprising determining the disease progression rate of a subject prior to starting the subject on a regimen of administration of a chlorite salt. In some embodiments, the disease progression rate can be determined by determining the rate of loss of an ALS functional rating metric prior to the starting of the subj ect on the regimen of administration of a chlorite salt. In some embodiments, the disease progression rate is as determined by the rate of loss of ALSFRS-R score. In some embodiments, a subject can be characterized as having no disease progression, slow disease progression, or fast disease progression rate based on the rate of loss of ALSFRS-R. In some embodiments, a subject characterized as having no disease progression has a disease progression rate of 0 units of ALSFRS-R lost / month. In some embodiments, a subject characterized as having a slow disease progression has a disease progression rate of less than 0.5 units of ALSFRS-R lost / month. In some embodiments, a subject characterized as having fast disease progression rate of greater than 0.5 units of ALSFRS-R lost / month. In some embodiments, the decision to start the subject on a regimen of administration of a chlorite salt is based at least in part on the disease progression rate of the subject. In some embodiments, a subject can be determined as having a disease progression rate of less than 0.5 units of ALSFRS-R lost / month and following the determining the subject can be started on a regimen of administration of a chlorite salt.

[0208] In some embodiments, the disclosure provides a method comprising determining the vital capacity of a subject prior to starting the subject on a regimen of administration of aWSGR Docket No. 59077-714.601 chlorite salt. In some embodiments, the vital capacity of the subject is the predicted vital capacity. In some embodiments, the subject has a predicted vital capacity of at least 60%, at least 65%, atleast70%, atleast75%, atleast 80%, atleast 85%, atleast 90%, atleast95%, or at least 99% prior to starting the subject on a regimen of administration of a chlorite salt. In some embodiments, the subject has a predicted vital capacity of at least 70% prior to starting the subject on a regimen of administration of a chlorite salt. In some embodiments, the subject has a predicted vital capacity of at least 80% prior to starting the subject on a regimen of administration of a chlorite salt.

[0209] In some embodiments, the subject experiences onset of ALS symptoms prior to starting the regimen of administration of a chlorite salt. In some embodiments, the subject experiences onset of ALS symptoms no more than 1 year, no more than 2 years, no more than 3 years, no more than 4 years, no more than 5 years, no more than 6 years, no more than 7 years, no more than 8 years, no more than 9 years, or no more than 10 years prior to starting the regimen of administration of a chlorite salt. In some embodiments, the subject experiences onset of ALS symptoms no more than 3 years prior to starting the regimen of administration of a chlorite salt.

[0210] In some embodiments, the subject has bulbar onset ALS. In some embodiments, the subject has limb-onset ALS.Creatinine

[0211] In some embodiments, the disclosure provides a method comprising starting a subject on a regimen of administration of a chlorite salt based at least in part on a level of creatinine observed in the subject. In some embodiments, the subject possesses a high-sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of theWSGR Docket No. 59077-714.601 regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0212] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising starting a subject on a regimen of administration of a chlorite salt based at least in part on a level of creatinine observed in the subject. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis.

[0213] In some embodiments, the disclosure provides a method comprising: a) observing that a subject has a serum creatinine level of less than 60 pmol / L; and b) based at least in part on the observing that a subject has a serum creatinine level of less than 60 pmol / L, starting the subject on a regimen of administration of a chlorite salt. In some embodiments, the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulationWSGR Docket No. 59077-714.601 comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0214] In some embodiments, the disclosure provides a method comprising: a) performing an assay on a subject to determine a serum creatinine level in the subject and observing that the serum creatinine level in the subject is lesser than 60 pmol / L; and b) based at least in part on the observing that the serum creatinine level in the subject is lesser than 60 pmol / L, starting the subject on a regimen of administration of a chlorite salt, wherein: the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically- acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically-acceptable excipient is dibasic sodium phosphate; the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the subject has amyotrophic lateral sclerosis. In some embodiments,WSGR Docket No. 59077-714.601 the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time. In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) observing that the subject has a serum creatinine level of less than 60 pmol / L; and b) based at least in part on the observing that a subject has a serum creatinine level of less than 60 pmol / L, starting the subject on a regimen of administration of a chlorite salt. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis.

[0215] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) performing an assay on the subject to determine a serum creatinine level and observing that the subject has a serum creatinine level of less than 60 pmol / L; and b) based at least in part on the observing that a subject has a serumWSGR Docket No. 59077-714.601 creatinine level of less than 60 pmol / L, starting the subject on a regimen of administration of a chlorite salt, wherein: the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically-acceptable excipient is dibasic sodium phosphate; the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the condition is amyotrophic lateral sclerosis.

[0216] In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time.

[0217] In some embodiments, the disclosure provides a method comprising continuing a regimen of administration of a chlorite salt in a subject who is undergoing the regimen based at least in part on a level of creatinine observed in the subject. In some embodiments, the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and onWSGR Docket No. 59077-714.601 each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0218] In some embodiments, the disclosure provides a method of treating a condition, the method comprising continuing a regimen of administration of a chlorite salt in a subject who is undergoing the regimen based at least in part on a level of creatinine observed in the subject. In some embodiments, the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0219] In some embodiments, the disclosure provides a method comprising: a) observing that a subject has a serum creatinine level of less than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt; and b) based at least in part on the observing that the subject has the serum creatinine level of less than 60 pmol / L, continuing the regimen. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt isWSGR Docket No. 59077-714.601 sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0220] In some embodiments, the disclosure provides a method comprising: a) performing an assay on a subject to determine a serum creatinine level in the subject and observing that the serum creatinine level is less than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt; and b) based at least in part on the observing that the subject has the serum creatinine level of less than 60 pmol / L, continuing the regimen, wherein: the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically-acceptable excipient is dibasic sodium phosphate; the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite saltbased on chlorite ion; the administration occurs on each of five consecutive daysWSGR Docket No. 59077-714.601 in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the subject has amyotrophic lateral sclerosis. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time.

[0221] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) observing that the subject has a serum creatinine level of less than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt that is therapeutically -effective for the condition; and b) based at least in part on the observing that the subject has a serum creatinine level of less than 60 pmol / L, continuing the regimen of the chlorite salt. In some embodiments, the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis.WSGR Docket No. 59077-714.601

[0222] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) performing an assay on the subject to determine a serum creatinine level in the subject and observing that the subject has a serum creatinine level of less than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt that is therapeutically -effective for the condition; and b) based at least in part on the observing that the subject has a serum creatinine level of less than 60 pmol / L, continuing the regimen of the chlorite salt, wherein: the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically - acceptable excipient is dibasic sodium phosphate; the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the condition is amyotrophic lateral sclerosis. In some embodiments, the method further comprises performing a second assay on the subject after passage of a period of time of at least one month after observing that the subject has the serum creatinine level of less than 60 pmol / L to determine a second serum creatinine level in the subject, wherein the second serum creatinine level shows an increase in serum creatinine level over the period of time.

[0223] In some embodiments, the disclosure provides a method comprising discontinuing a regimen of a chlorite salt in a subject who is undergoing the regimen of the chlorite salt based at least in part on a level of creatinine observed in the subject. In some embodiments, the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is byWSGR Docket No. 59077-714.601 infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of greater than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0224] In some embodiments, the disclosure provides a method comprising: a) observing that a subject has a serum creatinine level of greater than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt; and b) based at least in part on the observing that the subject has the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis.

[0225] In some embodiments, the disclosure provides a method comprising: a) performing an assay on a subject to determine a serum creatinine level in the subject and observing that theWSGR Docket No. 59077-714.601 serum creatinine level is greater than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt; and b) based at least in part on the observing that the subject has the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen, wherein: the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically-acceptable excipient is dibasic sodium phosphate; the chlorite saltis present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the subject has amyotrophic lateral sclerosis.

[0226] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) observing that the subject has a serum creatinine level of greater than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt that is therapeutically -effective for the condition; and b) based at least in part on the observing that the subject has a serum creatinine level of greater than 60 pmol / L, discontinuing the regimen of the chlorite salt. In some embodiments, the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments,WSGR Docket No. 59077-714.601 the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the serum creatinine level. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis.

[0227] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) performing an assay on the subject to determine a serum creatinine level in the subject and observing that the subject has a serum creatinine level of greater than 60 pmol / L, wherein the subject is undergoing a regimen of administration of a chlorite salt that is therapeutically -effective for the condition; and b) based at least in part on the observing that the subject has a serum creatinine level of greater than 60 pmol / L, discontinuing the regimen of the chlorite salt, wherein: the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; the chlorite salt is sodium chlorite; the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient; the pharmaceutical formulation has a pH from 7.5 to 9.5; the pharmaceutically-acceptable excipient is dibasic sodium phosphate; the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; the pharmaceutical formulation has a volume of about 250 mL; the administration is by infusion over about 30 to about 60 minutes; the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; the subject is human; and the condition is amyotrophic lateral sclerosis.

[0228] In some embodiments, the disclosure provides a method comprising monitoring a level of creatinine in a subject over a period of time, wherein the period of time is at least one month, and starting the subject on a regimen of administration of a chlorite salt based at least in part on the monitoring. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In someWSGR Docket No. 59077-714.601 embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis. In some embodiments, the method further comprises after the period of time observing that the subject exhibits a serum creatinine level of greater than 60 pmol / L, and based at least in part on the observing that the subject exhibits the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen.

[0229] In some embodiments, the disclosure provides a method of treating a condition, the method comprising monitoring a level of creatinine in a subject over a period of time, wherein the period of time is at least one month, and starting the subject on a regimen of administration of a chlorite salt for treatment of the condition based at least in part on the monitoring. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the creatinine level. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In someWSGR Docket No. 59077-714.601 embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis. In some embodiments, the method further comprises after the period of time observing that the subject exhibits a serum creatinine level of greater than 60 pmol / L, and based at least in part on the observing that the subject exhibits the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen.

[0230] In some embodiments, the disclosure provides a method comprising monitoring a level of creatinine in a subject over a period of time, wherein the period of time is at least one month, wherein the subject is undergoing a regimen of administration of a chlorite salt. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration i s by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the level of creatinine. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis. In some embodiments, the method further comprises after the period of time observing that the subject exhibits a serum creatinine level of greater than 60 pmol / L, and based at least in part on the observing that the subject exhibits the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen.

[0231] In some embodiments, the disclosure provides a method of treating a condition, the method comprising monitoring a level of creatinine in a subject over a period of time, wherein the period of time is at least one month, wherein the subject is undergoing a regimen of administration of a chlorite salt for the condition. In some embodiments, the subject possesses aWSGR Docket No. 59077-714.601 high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine the creatinine level. In some embodiments, the level of creatinine observed in the subject is a serum creatinine level of less than 60 pmol / L. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis. In some embodiments, the method further comprises after the period of time observing that the subject exhibits a serum creatinine level of greater than 60 pmol / L, and based at least in part on the observing that the subject exhibits the serum creatinine level of greater than 60 pmol / L, discontinuing the regimen.

[0232] In some embodiments, the disclosure provides a method comprising: a) determining that a subject has a serum creatinine level of less than 60 pmol / L; b) based at least in part on a), beginning the subject on a regimen of administration of a chlorite salt; and c) after beginning the subject on the regimen of the chlorite salt, determining that the subject has a serum creatinine level of greater than 60 pmol / L. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, theWSGR Docket No. 59077-714.601 administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing a first assay on the subject to determine that the subject has the serum creatinine level of less than 60 pmol / L, and performing a second assay on the subject to determine that the subject has the serum creatinine level of greater than 60 pmol / L. In some embodiments, the subject has a neurodegenerative condition. In some embodiments, the subject has amyotrophic lateral sclerosis. In some embodiments, the method further comprises discontinuing the regimen based at least in part on the determining that the subject has the serum creatinine level of greater than 60 pmol / L.

[0233] In some embodiments, the disclosure provides a method of treating a condition in a subject in need thereof, the method comprising: a) starting the subject on a regimen of administration of a chlorite salt; and b) after administering to the subject the therapeutically- effective amount of the chlorite salt, determining that the subject has a serum creatinine level of greater than 60 pmol / L. In some embodiments, the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine that the subject has a serumWSGR Docket No. 59077-714.601 creatinine level of greater than 60 pmol / L. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis. In some embodiments, the method further comprises discontinuing the regimen based at least in part on the determining that the subject has the serum creatinine level of greater than 60 pmol / L.

[0234] In some embodiments, the disclosure provides a method of treating a condition, the method comprising: a) determining that a subject has a serum creatinine level of less than 60 pmol / L; b) based at least in part on the determining that a subject has a serum creatinine level of less than 60 pmol / L, beginning the subject on a regimen of administration of a chlorite salt; c) determining a first vital capacity level of the subject at a first time point in the regimen; and d) determining a second vital capacity level of the subject at a second time point in the regimen that is at least one month after the first time point, wherein a change from the first vital capacity level to the second vital capacity level is lesser than would be observed in an analogous subject who is not on the regimen. In some embodiments, the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically -acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, wherein the method further comprises performing an assay on the subject to determine that the subject has a serum creatinine level of less than 60 pmol / L. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis.

[0235] In some embodiments, the disclosure provides a method of treating a condition, the method comprising: a) determining that a subject has a serum creatinine level of less than 60WSGR Docket No. 59077-714.601 pmol / L; b) based at least in part on the determining that a subject has a serum creatinine level of less than 60 pmol / L, starting the subject on a regimen of administration of a chlorite salt; and c) after beginning the subject on the regimen of administration of the chlorite salt, determining a score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale during at least a portion of the regimen. In some embodiments, the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay. In some embodiments, the chlorite salt is sodium chlorite. In some embodiments, the administration is of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient. In some embodiments, the pharmaceutical formulation has a pH from 7.5 to 9.5. In some embodiments, the pharmaceutically-acceptable excipient is dibasic sodium phosphate. In some embodiments, the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM. In some embodiments, the pharmaceutical formulation has a volume of about 250 mL. In some embodiments, the administration is oral. In some embodiments, the administration is parenteral. In some embodiments, the administration is by infusion over about 30 to about 60 minutes. In some embodiments, the administration is by infusion over about 30 minutes. In some embodiments, the administration is of about 2 mg / kg subject body mass of the chlorite saltbased on chlorite ion. In some embodiments, the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen. In some embodiments, the subject is human. In some embodiments, the method further comprises performing an assay on the subject to determine that the subject has a serum creatinine level of less than 60 pmol / L. In some embodiments, the condition is a neurodegenerative condition. In some embodiments, the condition is amyotrophic lateral sclerosis. In some embodiments, the method further comprises, at least a month after c), determining a second score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, wherein a change from the first score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale to the second score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale is lesser than would be observed in an analogous subject who is not on the regimen of the agent that is therapeutically effective for the condition. In some embodiments, the method further comprises, at least a month after c), determining a second score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, wherein a change from the first score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale to the second score of the subject based on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale is lesser than would be observed had the subject who not started the regimen.WSGR Docket No. 59077-714.601

[0236] In some embodiments, the disclosure provides a method of treating amyotrophic lateral sclerosis (ALS) in a subject in need thereof, the method comprising: (a) determining that the subject exhibits a serum creatinine level that is lesser than 60 mg / L; (b) subsequent to the determining that the subject exhibits a serum creatinine level that is lesser than 60 mg / L, starting the subject on a therapeutically -effective regimen of sodium chlorite, wherein the therapeutically -effective regimen of sodium chlorite is infusion of an aqueous formulation of 2 mg / kg of sodium chlorite based on chlorite ion on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen; and (c) monitoring the serum creatinine level while the subject is on the therapeutically -effective regimen of sodium chlorite, wherein, in a clinical study, wherein the clinical study comprises a first test group, a first placebo group, a second test group, and a second placebo group; wherein each member of the first test group has ALS, has a blood level of c-reactive protein of at least 1.13 mg / L, and has a serum creatinine level that is lesser than 60 mg / L; wherein each member of the first placebo group has ALS, has a blood level of c-reactive protein of at least 1.13 mg / L, and has a serum creatinine level that is lesser than 60 mg / L; wherein each member of the second test group has ALS, has a blood level of c-reactive protein of at least 1.13 mg / L, and has a seium creatinine level that is greater than 60 mg / L; and wherein each member of the second placebo group has ALS, has a blood level of c-reactive protein of at least 1.13 mg / L, and has a serum creatinine level that is greater than 60 mg / L; wherein the clinical study begins on day zero and ends six months from day zero, if on day zero: a baseline vital capacity of each member of the first test group is independently determined by spirometry; a baseline vital capacity of each member of the first placebo group is independently determined by spirometry; a baseline vital capacity of each member of the second test group is independently determined by spirometry; a baseline vital capacity of each member of the second placebo group is independently determined by spirometry; each member of the first test group begins the therapeutically -effective regimen of sodium chlorite; each member of the first placebo group begins a regimen of placebo; each member of the second test group begins the therapeutically -effective regimen of sodium chlorite; and each member of the second placebo group begins a regimen of placebo; subsequent to day zero: an additional vital capacity of each member of the first test group is independently determined by spirometry at six months from day zero; an additional vital capacity of each member of the first placebo group is independently determined by spirometry at six months from day zero; an additional vital capacity of each member of the second test group is independently determined by spirometry at six months from day zero; and an additional vital capacity of each member of the second placebo group is independently determined by spirometry at six months from day zero; and a percent change from baseline vital capacity isWSGR Docket No. 59077-714.601 determined for the first test group at six months from day zero; a percent change from baseline vital capacity is determined for the first placebo group at six months from day zero; a percent change from baseline vital capacity is determined for the second test group at six months from day zero; and a percent change from baseline vital capacity is determined for the second placebo group at six months from day zero; then the percent change from baseline vital capacity for the first test group at six months from day zero; the percent change from baseline vital capacity for the second test group at six months from day zero; and the percent change from baseline vital capacity for the second placebo group at six months from day zero are all within a margin of error of one another; and the percent change from baseline vital capacity for the first placebo group at six months from day zero is: a negative value that is larger in magnitude than is the percent change from baseline vital capacity for the first test group at six months from day zero to a degree having statistical significance; a negative value that is larger in magnitude than is the percent change from baseline vital capacity for the second test group at six months from day zero to a degree having statistical significance; and a negative value that is larger in magnitude than is the percent change from baseline vital capacity for the second placebo group at six months from day zero to a degree having statistical significance.Bio markers

[0237] In some embodiments, the method comprises determining the baseline level of a biomarker in a subject prior to starting the regimen of administration of a chlorite salt. In some embodiments, the method comprises determining the level of a biomarker after administering the regimen of administration of a chlorite salt. In some embodiments, the determining of the level of the biomarker is by assay. In some embodiments, the determining of the level of the biomarker is by assay of a plasma or blood sample obtained from the subject. Non-limiting examples of assay include enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunoassay, and chemiluminescent enzyme immunoassay (CLEIA). In some embodiments, method comprises determining the change in biomarker level from baseline. In some embodiments, the determining the change in biomarker level from baseline comprises determining the difference between biomarker levels after administering the regimen of administration of a chlorite salt and the baseline level of the biomarker. In some embodiments, the change in biomarker level from baseline is a decrease in the biomarker level. In some embodiments, the change in biomarker level is an increase in the biomarker level.

[0238] In some embodiments, the method further comprises determining the baseline change in neurofilament light chain (NfL) levels following administration of a regimen of a chlorite salt. In some embodiments, administration of a regimen of a chlorite salt results in a decrease in NfL levels in a subject. In some embodiments, administration of a regimen of a chlorite salt results inWSGR Docket No. 59077-714.601 an at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8% at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 25%, or at least 30% decrease in NfL levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 5% decrease in NfL levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 10% decrease in NfL levels from baseline.

[0239] In some embodiments, the method further comprises determining the baseline change in interleukin- 18 (IL-18) levels following administration of a regimen of a chlorite salt. In some embodiments, administration of a regimen of a chlorite salt results in a decrease in IL-18 levels in a subject. In some embodiments, administration of a regimen of a chlorite salt results in an at at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, atleast 90%, at least 95%, at least 99%, or at least 100% decrease in IL- 18 levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 25% decrease in IL-18 levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 50% decrease in IL-18 levels from baseline.

[0240] In some embodiments, the method further comprises determining the baseline change in hepatocyte growth factor (HGF) levels following administration of a regimen of a chlorite salt. In some embodiments, administration of a regimen of a chlorite salt results in a decrease in HGF levels in a subject. In some embodiments, administration of a regimen of a chlorite salt results in an at at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or at least 100% decrease in HGF levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 10% decrease in HGF levels from baseline. In some embodiments, administration of a regimen of a chlorite salt results in an at least 25% decrease in HGF levels from baseline.

[0241] In some embodiments, the administration of a regimen of a chlorite salt is based in part on the baseline levels of the biomarker in the subject. In some embodiments, a subject can be stratified in a treatment group based in part on the baseline levels of the biomarker in the subject. In some embodiments, the stratification comprises determining median level of the biomarker in a population of subjects. In some embodiments, the stratification comprises determiningthe baseline biomarker level of the subject and comparing the baseline biomarkerWSGR Docket No. 59077-714.601 level of the subject to the median biomarker level in a population of subjects. In some embodiments, the method comprises administering a regimen of chlorite salt to a subject with a baseline level of a biomarker that is less than the median biomarker level. In some embodiments, the method comprises administering a regimen of a chlorite salt to a subject with a baseline level of a biomarker that is greater than the median biomarker level. In some embodiments, the biomarker comprises NfL.EMBODIMENTS

[0242] The following embodiments are illustrative and do not limit the scope of the invention.

[0243] Embodiment Al . A method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt.

[0244] Embodiment A2. The method of embodiment Al, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0245] Embodiment A3. The method of embodiment Al, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0246] Embodiment A4. The method of any one of embodiments Al -A3, wherein the chlorite salt is sodium chlorite.

[0247] Embodiment A5. The method of any one of embodiments A1 -A4, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient.

[0248] Embodiment A6. The method of embodiment A5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0249] Embodiment A7. The method of any one of embodiments A5-A6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0250] Embodiment A8. The method of any one of embodiments A5-A7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0251] Embodiment A9. The method of any one of embodiments A5 -A8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.WSGR Docket No. 59077-714.601

[0252] Embodiment A10. The method of any one of embodiments A5-A9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0253] Embodiment Al 1. The method of any one of embodiments Al -A10, wherein the administrations of the chlorite salt are oral.

[0254] Embodiment A12. The method of any one of embodiments Al -Al 1, wherein the administrations of the chlorite salt are parenteral.

[0255] Embodiment Al 3. The method of any one of embodiments Al -Al 2, wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes.

[0256] Embodiment A14. The method of any one of embodiments Al -A13, wherein the administrations of the chlorite salt are by infusion over about 30 minutes.

[0257] Embodiment Al 5. The method of any one of embodiments Al -Al 4, wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0258] Embodiment Al 6. The method of any one of embodiments Al -Al 5, wherein the administrations of the chlorite salt occur on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0259] Embodiment Al 7. The method of any one of embodiments Al -Al 5, wherein the administrations of the chlorite salt occur about every other day.

[0260] Embodiment Al 8. The method of any one of embodiments Al -Al 5, wherein the administrations of the chlorite salt occur about every day.

[0261] Embodiment Al 9. The method of any one of embodiments Al -Al 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0262] Embodiment A20. The method of any one of embodiments Al -Al 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least six months.

[0263] Embodiment A21. The method of any one of embodiments Al -Al 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twelve months.

[0264] Embodiment A22. The method of any one of embodiments Al -Al 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twenty -four months.

[0265] Embodiment A23. The method of any one of embodiments Al -Al 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting until death of the subject.WSGR Docket No. 59077-714.601

[0266] Embodiment A24. The method of any one of embodiments Al -A23, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of the analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least about 4.8 months.

[0267] Embodiment A25. The method of any one of embodiments Al and A4-A23, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of the analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least about 20 months, wherein the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0268] Embodiment A26. A method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least about 4.8 months, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0269] Embodiment A27. A method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt by at least about 20 months, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay; wherein each administration of the chlorite saltWSGR Docket No. 59077-714.601 comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0270] EmbodimentBl. A method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically - effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt.

[0271] Embodiment B2. The method of embodiment Bl, wherein the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0272] Embodiment B3. The method of embodiment Bl, wherein the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0273] EmbodimentB4. The method of any one of embodiments Bl -B3, wherein the chlorite salt is sodium chlorite.

[0274] Embodiment B5. The method of any one of embodiments B1 -B4, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically- acceptable excipient.

[0275] Embodiment B6. The method of embodiment B5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0276] Embodiment B7. The method of any one of embodiments B5-B6, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.

[0277] Embodiment B8. The method of any one of embodiments B5-B7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0278] Embodiment B9. The method of any one of embodiments B5-B8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.WSGR Docket No. 59077-714.601

[0279] Embodiment BIO. The method of any one of embodiments B5-B9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0280] Embodiment Bl 1. The method of any one of embodiments Bl -B10, wherein the administrations of the chlorite salt are oral.

[0281] Embodiment Bl 2. The method of any one of embodiments Bl -Bl 1, wherein the administrations of the chlorite salt are parenteral.

[0282] Embodiment Bl 3. The method of any one of embodiments Bl -Bl 2, wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes.

[0283] Embodiment Bl 4. The method of any one of embodiments B1 -B13, wherein the administrations of the chlorite salt are by infusion over about 30 minutes.

[0284] Embodiment Bl 5. The method of any one of embodiments Bl -Bl 4, wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0285] Embodiment Bl 6. The method of any one of embodiments Bl -Bl 5, wherein the administrations of the chlorite salt occur on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0286] Embodiment Bl 7. The method of any one of embodiments Bl -Bl 5, wherein the administrations of the chlorite salt occur about every other day.

[0287] Embodiment Bl 8. The method of any one of embodiments B1 -B15, wherein the administrations of the chlorite salt occur about every day.

[0288] Embodiment Bl 9. The method of any one of embodiments Bl -Bl 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0289] Embodiment B20. The method of any one of embodiments Bl -B19, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least six months.

[0290] Embodiment B21. The method of any one of embodiments Bl -Bl 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twelve months.

[0291] Embodiment B22. The method of any one of embodiments Bl -Bl 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twenty -four months.

[0292] Embodiment B23. The method of any one of embodiments Bl -Bl 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting until death of the subject.WSGR Docket No. 59077-714.601

[0293] Embodiment B24. The method of any one of embodiments Bl -B23, wherein the therapeutically -effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of the analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically -effective regimen of the chlorite salt by at least 0.05.

[0294] Embodiment B25. A method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically - effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt by at least 0.05, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about2 mg / kg subjectbody massof the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0295] Embodiment Cl . The method of any of the foregoing embodiments, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo-controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high -sensitivity C-reactive protein (hs-CRP) concentration of > 0.113 mg / dL prior to the placebo-controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo -controlled study estimates overall survival of the study subjects by Kaplan-Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kgWSGR Docket No. 59077-714.601 sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo- controlled study estimates median survival of: i) 2.7 years for all study subjects receiving 2 mg / kg sodium chlorite based on chlorite ion with a 95% confidence interval of 2.4 to 3.5; ii) 2.3 years for all study subjects receiving normal saline as placebo with a 95% confidence interval of 1.8 to 2.9; iii) 3.3 years for all study subjects under age 65 receiving 2 mg / kg sodium chlorite based on chlorite ion with a 95% confidence interval of 2.4 to 3.9; and iv) 2.4 years for all study subjects under age 65 receiving normal saline as placebo with a 95% confidence interval of 1.7 to 3.3.

[0296] Embodiment DI . A method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma neurofilament light chain level of the subject based on a blood assay; c) sub sequent to the obtaining the first plasma neurofilament light chain level of the subject, obtaining a second plasma neuro filament light chain level of the subject based on a blood assay; d) determining that the second plasma neurofilament light chain level of the subject is a decrease of at least ten percent in comparison to the first plasma neurofilament light chain level of the subject; and e) based at least in part on the determining that the second plasma neurofilament light chain level of the subject is a decrease of at least ten percent in comparison to the first plasma neurofilament light chain level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0297] Embodiment D2. The method of embodiment DI, wherein the blood assay is a quantification of neurofilament light chain levels in blood of the subject by high performance liquid chromatography.

[0298] Embodiment D3. The method of any one of embodiments DI -D2, wherein the obtaining the first plasma neurofilament light chain level of the subject based on the blood assay comprises performing the blood assay; and the obtaining the second plasma neurofilament light chain level of the subject based on the blood assay comprises performing the blood assay.

[0299] EmbodimentD4. The method of any one of embodiments DI -D3, wherein the chlorite salt is sodium chlorite.WSGR Docket No. 59077-714.601

[0300] Embodiment D5. The method of any one of embodiments DI -D4, wherein the regimen of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient.

[0301] Embodiment D6. The method of embodiment D5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0302] Embodiment D7. The method of any one of embodiments D5-D6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0303] Embodiment D8. The method of any one of embodiments D5-D7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0304] EmbodimentD9. The method of any one of embodiments D5-D8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0305] Embodiment D10. The method of any one of embodiments D5-D9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0306] Embodiment DI 1. The method of any one of embodiments DI -D10, wherein the administration is oral.

[0307] Embodiment D12. The method of any one of embodiments DI -DI 1, wherein the administration is parenteral.

[0308] Embodiment D13. The method of any one of embodiments DI -D12, wherein the administration of the chlorite salt is by infusion over about 30 to about 60 minutes.

[0309] Embodiment D14. The method of any one of embodiments DI -D13, wherein the administration of the chlorite salt is by infusion over about 30 minutes.

[0310] Embodiment DI 5. The method of any one of embodiments DI -DI 4, wherein the administration of the chlorite salt is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0311] Embodiment DI 6. The method of any one of embodiments DI -DI 5, wherein the administration of the chlorite salt occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0312] Embodiment D17. The method of any one of embodiments DI -D15, wherein the administration of the chlorite salt occurs about every other day.

[0313] Embodiment DI 8. The method of any one of embodiments DI -DI 5, wherein the administration of the chlorite salt occurs about every day.

[0314] Embodiment D19. The method of any one of embodiments DI -D18, wherein the subject had taken riluzole prior to beginning the regimen.WSGR Docket No. 59077-714.601

[0315] Embodiment D20. The method of any one of embodiments DI -D19, wherein the regimen of administration of the chlorite salt lasts at least six months.

[0316] Embodiment D21. The method of any one of embodiments DI -DI 9, wherein the regimen of administration of the chlorite salt lasts at least twelve months.

[0317] Embodiment D22. The method of any one of embodiments DI -D19, wherein the regimen of administration of the chlorite salt lasts at least twenty -four months.

[0318] Embodiment D23. The method of any one of embodiments DI -DI 9, wherein the regimen of administration of the chlorite salt lasts until death of the subject.

[0319] Embodiment D24. The method of any one of embodiments D1 -D23, wherein the regimen of administration of the chlorite salt is about 0.2 mg / kg / day to about 3.5 mg / kg / day.

[0320] Embodiment El . A method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically - effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt by at least 0.05, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0321] EmbodimentFl. A method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically-effective regimen comprises a course of administrations of the chlorite salt spanning at least a year.

[0322] Embodiment F2. The method of embodiment Fl, wherein the subject possesses a high- sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0323] EmbodimentF3. The method of any one of embodiments F1-F2, wherein the chlorite salt is sodium chlorite.WSGR Docket No. 59077-714.601

[0324] Embodiment F4. The method of any one of embodiments F1-F3, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient.

[0325] Embodiment F5. The method of embodiment F4, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0326] Embodiment F6. The method of any one of embodiments F4-F5, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0327] Embodiment F7. The method of any one of embodiments F4-F6, wherein the pharmaceutical formulation is substantially free of preservatives.

[0328] Embodiment F8. The method of any one of embodiments F4-F7, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0329] Embodiment F9. The method of any one of embodiments F4-F8, wherein the pharmaceutical formulation has a volume of about 250 mL.

[0330] Embodiment F10. The method of any one of embodiments F1-F9, wherein the administrations of the chlorite salt are oral.

[0331] Embodiment Fl 1. The method of any one of embodiments F1-F10, wherein the administrations of the chlorite salt are parenteral.

[0332] Embodiment F12. The method of any one of embodiments Fl-Fl 1, wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes.

[0333] Embodiment Fl 3. The method of any one of embodiments F1-F12, wherein the administrations of the chlorite salt are by infusion over about 30 minutes.

[0334] Embodiment Fl 4. The method of any one of embodiments F1-F13, wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0335] Embodiment Fl 5. The method of any one of embodiments F1-F14, wherein the administrations of the chlorite salt occur on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0336] Embodiment Fl 6. The method of any one of embodiments F1-F14, wherein the administrations of the chlorite salt occur about every other day.

[0337] Embodiment Fl 7. The method of any one of embodiments F1-F14, wherein the administrations of the chlorite salt occur about every day.

[0338] Embodiment Fl 8. The method of any one of embodiments Fl -Fl 7, wherein the subject had taken riluzole prior to beginning the regimen.

[0339] Embodiment Fl 9. The method of any one of embodiments F1-F18, wherein theWSGR Docket No. 59077-714.601 therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least about two years.

[0340] Embodiment F20. A method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least about a year, wherein the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0341] Embodiment G1. A method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject.

[0342] Embodiment G2. The method of embodiment Gl, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0343] Embodiment G3. The method of any one of embodiments Gl -G2, wherein the chlorite salt is sodium chlorite.

[0344] Embodiment G4. The method of any one of embodiments G1-G3, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically- acceptable excipient.

[0345] Embodiment G5. The method of embodiment G4, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0346] Embodiment G6. The method of any one of embodiments G4-G5, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.

[0347] Embodiment G7. The method of any one of embodiments G4-G6, wherein the pharmaceutical formulation is substantially free of preservatives.WSGR Docket No. 59077-714.601

[0348] Embodiment G8. The method of any one of embodiments G4-G7, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0349] Embodiment G9. The method of any one of embodiments G4-G8, wherein the pharmaceutical formulation has a volume of about 250 m .

[0350] Embodiment G10. The method of any one of embodiments G1-G9, wherein the administrations of the chlorite salt are oral.

[0351] Embodiment G11. The method of any one of embodiments G1-G10, wherein the administrations of the chlorite salt are parenteral.

[0352] Embodiment G12. The method of any one of embodiments Gl-Gl 1, wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes.

[0353] Embodiment G13. The method of any one of embodiments Gl-Gl 2, wherein the administrations of the chlorite salt are by infusion over about 30 minutes.

[0354] Embodiment G14. The method of any one of embodiments Gl-Gl 3, wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0355] Embodiment G15. The method of any one of embodiments Gl-Gl 4, wherein the administrations of the chlorite salt occur on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0356] Embodiment G16. The method of any one of embodiments Gl-Gl 4, wherein the administrations of the chlorite salt occur about every other day.

[0357] Embodiment G17. The method of any one of embodiments Gl-Gl 4, wherein the administrations of the chlorite salt occur about every day.

[0358] Embodiment G18. The method of any one of embodiments Gl-Gl 7, wherein the subject had taken riluzole prior to beginning the regimen.

[0359] Embodiment G19. The method of any one of embodiments Gl-Gl 8, wherein the determining a vital capacity of the subject comprises spirometry.

[0360] Embodiment G20. A method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically-effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject by spirometry, wherein the subject possesses a high -sensitivity C- reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient; wherein the pharmaceutical formulation has a pH fromWSGR Docket No. 59077-714.6017.5 to 9.5; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administrations of the chlorite salt are by infusion over about 30 to about 60 minutes; wherein the administrations of the chlorite salt are of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion; and wherein the chlorite salt is sodium chlorite.

[0361] Embodiment Hl . A method comprising increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject, wherein at baseline, the subject demonstrates ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo -controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high- sensitivity C-reactive protein (hs-CRP) concentration of > 0. 113 mg / dL prior to the placebo- controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo - controlled study estimates overall survival of the study subjects by Kaplan -Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo-controlled study estimates median survival of: i) 29 months for all study subjects receiving placebo and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry; and ii) 48 months for all study subjects receiving 2 mg / kg sodium chlorite based on chlorite ion and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry.

[0362] Embodiment H2. The method of embodiment Hl, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.WSGR Docket No. 59077-714.601

[0363] Embodiment H3. The method of embodiment Hl, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0364] Embodiment H4. The method of any one of embodiments H1-H3, wherein the chlorite salt is sodium chlorite.

[0365] Embodiment H5. The method of any one of embodiments H1 -H4, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient.

[0366] Embodiment H6. The method of embodiment H5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0367] Embodiment H7. The method of any one of embodiments H5-H6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0368] Embodiment H8. The method of any one of embodiments H5-H7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0369] Embodiment H9. The method of any one of embodiments H5-H8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0370] Embodiment H10. The method of any one of embodiments H5-H9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0371] Embodiment Hl 1. The method of any one of embodiments H1 -H10, wherein the administering is oral.

[0372] Embodiment H12. The method of any one of embodiments Hl -Hl 1, wherein the administering is parenteral.

[0373] Embodiment Hl 3. The method of any one of embodiments H1 -H12, wherein the administering is by infusion over about 30 to about 60 minutes.

[0374] Embodiment H14. The method of any one of embodiments H1 -H13, wherein the administering is by infusion over about 30 minutes.

[0375] Embodiment Hl 5. The method of any one of embodiments H1 -H14, wherein the administering is about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0376] Embodiment Hl 6. The method of any one of embodiments Hl -Hl 5, wherein the administering is on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0377] Embodiment Hl 7. The method of any one of embodiments Hl -Hl 5, wherein the administering is about every other day.WSGR Docket No. 59077-714.601

[0378] Embodiment Hl 8. The method of any one of embodiments H1 -H15, wherein the administering is about every day.

[0379] Embodiment Hl 9. The method of any one of embodiments Hl -Hl 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0380] Embodiment H20. The method of any one of embodiments Hl -H19, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least six months.

[0381] Embodiment H21 . The method of any one of embodiments Hl -Hl 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twelve months.

[0382] Embodiment H22. The method of any one of embodiments Hl -H19, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twenty -four months.

[0383] Embodiment H23. The method of any one of embodiments Hl -Hl 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting until death of the subject.

[0384] Embodiment II . A method comprising increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject, wherein at baseline, the subject demonstrates ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo -controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high- sensitivity C-reactive protein (hs-CRP) concentration of > 0. 113 mg / dL prior to the placebo- controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo - controlled study estimates overall survival of the study subjects by Kaplan -Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the secondWSGR Docket No. 59077-714.601 time point is death or termination of the placebo -controlled study, whichever occurs first, then the placebo-controlled study estimates median survival of: i) 29 months for all study subjects receiving placebo and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry; and ii) 42 months for all study subjects receiving 2 mg / kg sodium chlorite based on chlorite ion and having baseline ALSFRS-R loss of less than 0.5 ALSFRS-R units / month as determined by respirometry.

[0385] Embodiment 12. The method of embodiment II, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0386] Embodiment 13. The method of embodiment II, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0387] Embodiment 14. The method of any one of embodiments II -13, wherein the chlorite salt is sodium chlorite.

[0388] Embodiment 15. The method of any one of embodiments 11 -14, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient.

[0389] Embodiment 16. The method of embodiment 15, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0390] Embodiment 17. The method of any one of embodiments 15-16, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0391] Embodiment 18. The method of any one of embodiments 15-17, wherein the pharmaceutical formulation is substantially free of preservatives.

[0392] Embodiment 19. The method of any one of embodiments 15-18, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0393] Embodiment 110. The method of any one of embodiments 15-19, wherein the pharmaceutical formulation has a volume of about 250 mL.

[0394] Embodiment II 1. The method of any one of embodiments II -110, wherein the administering is oral.

[0395] Embodiment 112. The method of any one of embodiments II -Il l, wherein the administering is parenteral.

[0396] Embodiment 113. The method of any one of embodiments 11 -112, wherein the administering is by infusion over about 30 to about 60 minutes.WSGR Docket No. 59077-714.601

[0397] Embodiment 114. The method of any one of embodiments 11 -113, wherein the administering is by infusion over about 30 minutes.

[0398] Embodiment 115. The method of any one of embodiments 11 -114, wherein the administering is about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0399] Embodiment 116. The method of any one of embodiments 11 -115, wherein the administering is on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0400] Embodiment 117. The method of any one of embodiments 11 -115, wherein the administering is about every other day.

[0401] Embodiment 118. The method of any one of embodiments 11 -115, wherein the administering is about every day.

[0402] Embodiment 119. The method of any one of embodiments 11 -118, wherein the subject had taken riluzole prior to beginning the regimen.

[0403] Embodiment 120. The method of any one of embodiments 11 -119, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least six months.

[0404] Embodiment 121. The method of any one of embodiments 11 -119, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twelve months.

[0405] Embodiment 122. The method of any one of embodiments 11 -119, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twenty -four months.

[0406] Embodiment 123. The method of any one of embodiments 11 -119, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting until death of the subject.

[0407] Embodiment JI . A method comprising reducing vital capacity loss of a subject in need of treatment for amyotrophic lateral sclerosis (ALS) by administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt reduces vital capacity loss of the subject, wherein at baseline, the subject demonstrates greaterthan 80% vital capacity and ALSFRS-R loss of less than 0.57 ALSFRS-R units / month as determinedby respirometry, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo-controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high-sensitivity C-reactive protein (hs-CRP) concentration of > 0.113 mg / dL priorto the placebo-controlled study; about 115 of the study subjects received 2WSGR Docket No. 59077-714.601 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo-controlled study estimates overall survival of the study subjects by Kaplan-Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo -controlled study, whichever occurs first, then the placebo-controlled study estimates that the study subjects demonstrate a slowing of 43% to 55% of loss of vital capacity compared to the subjects receiving placebo as determined by respirometry.

[0408] Embodiment J2. The method of embodiment JI, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

[0409] Embodiment J3. The method of embodiment JI, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 3 mg / L as determined by a blood assay.

[0410] Embodiment J4. The method of any one of embodiments J1 -J3, wherein the chlorite salt is sodium chlorite.

[0411] Embodiment J5. The method of any one of embodiments J1 -J4, wherein each administration of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically - acceptable excipient.

[0412] Embodiment J6. The method of embodiment J5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0413] Embodiment J7. The method of any one of embodiments J5-J6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0414] Embodiment J8. The method of any one of embodiments J5-J7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0415] Embodiment J9. The method of any one of embodiments J5-J8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0416] Embodiment JI 0. The method of any one of embodiments J5-J9, wherein the pharmaceutical formulation has a volume of about 250 mL.WSGR Docket No. 59077-714.601

[0417] Embodiment JI 1. The method of any one of embodiments JI -JI 0, wherein the administering is oral.

[0418] Embodiment JI 2. The method of any one of embodiments JI -JI 1, wherein the administering is parenteral

[0419] Embodiment JI 3. The method of any one of embodiments JI -JI 2, wherein the administering is by infusion over about 30 to about 60 minutes.

[0420] Embodiment J14. The method of any one of embodiments JI -JI 3, wherein the administering is by infusion over about 30 minutes.

[0421] Embodiment JI 5. The method of any one of embodiments JI -JI 4, wherein the administering is about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0422] Embodiment J16. The method of any one of embodiments JI -JI 5, wherein the administering is on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0423] Embodiment J17. The method of any one of embodiments JI -JI 5, wherein the administering is about every other day.

[0424] Embodiment J18. The method of any one of embodiments JI -JI 5, wherein the administering is about every day.

[0425] Embodiment J19. The method of any one of embodiments JI -JI 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0426] Embodiment J20. The method of any one of embodiments JI -JI 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least six months.

[0427] Embodiment J21. The method of any one of embodiments JI -JI 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twelve months.

[0428] Embodiment J22. The method of any one of embodiments JI -JI 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting at least twenty -four months.

[0429] Embodiment J23. The method of any one of embodiments JI -JI 9, wherein the administering to the subject a therapeutically -effective regimen of a chlorite salt occurs over a regimen lasting until death of the subject.

[0430] Embodiment KI . A method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma IL-18 level of the subject based on a blood assay;WSGR Docket No. 59077-714.601 c) sub sequent to the obtaining the first plasma IL-18 level of the subject, obtaining a second IL- 10 level of the subject based on a blood assay; d) determining that the second plasma IL- 18 level of the subject is a decrease of at least ten percent in comparison to the first plasma IL-18 level of the subject; and e) based at least in parton the determining that the second plasma IL-18 level of the subject is a decrease of at least ten percent in comparison to the first plasma IL-18 level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0431] Embodiment K2. The method of embodiment KI, wherein the blood assay is a quantification of IL-18 levels in blood of the subject by high performance liquid chromatography.

[0432] Embodiment K3. The method of any one of embodiments KI -K2, wherein the obtaining the first plasma IL-18 level of the subject based on the blood assay comprises performing the blood assay; and the obtaining the second plasma IL-18 level of the subject based on the blood assay comprises performing the blood assay.

[0433] EmbodimentK4. The method of any one of embodiments KI -K3, wherein the chlorite salt is sodium chlorite.

[0434] Embodiment K5. The method of any one of embodiments KI -K4, wherein the regimen of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient.

[0435] Embodiment K6. The method of embodiment K5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0436] Embodiment K7. The method of any one of embodiments K5-K6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0437] Embodiment K8. The method of any one of embodiments K5-K7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0438] EmbodimentK9. The method of any one of embodiments K5-K8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0439] Embodiment K10. The method of any one of embodiments K5-K9, wherein the pharmaceutical formulation has a volume of about 250 mL.

[0440] Embodiment KI 1. The method of any one of embodiments KI -K10, wherein the administration is oral.

[0441] Embodiment KI 2. The method of any one of embodiments KI -KI 1, wherein the administration is parenteral.WSGR Docket No. 59077-714.601

[0442] Embodiment KI 3. The method of any one of embodiments KI -KI 2, wherein the administration of the chlorite salt is by infusion over about 30 to about 60 minutes.

[0443] Embodiment KI 4. The method of any one of embodiments KI -KI 3, wherein the administration of the chlorite salt is by infusion over about 30 minutes.

[0444] Embodiment KI 5. The method of any one of embodiments KI -KI 4, wherein the administration of the chlorite salt is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0445] Embodiment KI 6. The method of any one of embodiments KI -KI 5, wherein the administration of the chlorite salt occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0446] Embodiment KI 7. The method of any one of embodiments KI -KI 5, wherein the administration of the chlorite salt occurs about every other day.

[0447] Embodiment KI 8. The method of any one of embodiments KI -KI 5, wherein the administration of the chlorite salt occurs about every day.

[0448] Embodiment KI 9. The method of any one of embodiments KI -KI 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0449] Embodiment K20. The method of any one of embodiments KI -KI 9, wherein the regimen of administration of the chlorite salt lasts at least six months.

[0450] Embodiment K21. The method of any one of embodiments KI -KI 9, wherein the regimen of administration of the chlorite salt lasts at least twelve months.

[0451] Embodiment K22. The method of any one of embodiments K1-K19, wherein the regimen of administration of the chlorite salt lasts at least twenty -four months.

[0452] Embodiment K23. The method of any one of embodiments KI -KI 9, wherein the regimen of administration of the chlorite salt lasts until death of the subject.

[0453] Embodiment K24. The method of any one of embodiments K1 -K23, wherein the regimen of administration of the chlorite salt is about 0.2 mg / kg / day to about 3.5 mg / kg / day.

[0454] Embodiment LI. A method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma HGF level of the subject based on a blood assay; c) sub sequent to the obtaining the first plasma HGF level of the subj ect, obtaining a second plasma HGF level of the subject based on a blood assay; d) determining that the second plasma HGF level of the subject is a decrease of at least ten percent in comparison to the first plasma HGF level of the subject; andWSGR Docket No. 59077-714.601 e) based at least in part on the determining that the second plasma HGF level of the subject is a decrease of at least ten percent in comparison to the first plasma HGF level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0455] Embodiment L2. The method of embodiment LI, wherein the blood assay is a quantification of HGF levels in blood of the subject by high performance liquid chromatography.

[0456] Embodiment L3. The method of any one of embodiments LI -L2, wherein the obtaining the first plasma HGF level of the subject based on the blood assay comprises performing the blood assay; and the obtaining the second plasma HGF level of the subject based on the blood assay comprises performing the blood assay.

[0457] EmbodimentL4. The method of any one of embodiments LI -L3, wherein the chlorite salt is sodium chlorite.

[0458] Embodiment L5. The method of any one of embodiments L1 -L4, wherein the regimen of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient.

[0459] Embodiment L6. The method of embodiment L5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0460] Embodiment L7. The method of any one of embodiments L5-L6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0461] Embodiment L8. The method of any one of embodiments L5-L7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0462] EmbodimentL9. The method of any one of embodiments L5 -L8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0463] Embodiment L10. The method of any one of embodiments L5-L9, wherein the pharmaceutical formulation has a volume of about 250 mL.

[0464] Embodiment LI 1. The method of any one of embodiments LI -L10, wherein the administration is oral.

[0465] Embodiment L12. The method of any one of embodiments LI -LI 1, wherein the administration is parenteral.

[0466] Embodiment LI 3. The method of any one of embodiments LI -LI 2, wherein the administration of the chlorite salt is by infusion over about 30 to about 60 minutes.

[0467] Embodiment L14. The method of any one of embodiments LI -LI 3, wherein the administration of the chlorite salt is by infusion over about 30 minutes.WSGR Docket No. 59077-714.601

[0468] Embodiment LI 5. The method of any one of embodiments LI -LI 4, wherein the administration of the chlorite salt is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0469] Embodiment LI 6. The method of any one of embodiments LI -LI 5, wherein the administration of the chlorite salt occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regim en.

[0470] Embodiment LI 7. The method of any one of embodiments LI -LI 5, wherein the administration of the chlorite salt occurs about every other day.

[0471] Embodiment LI 8. The method of any one of embodiments LI -LI 5, wherein the administration of the chlorite salt occurs about every day.

[0472] Embodiment LI 9. The method of any one of embodiments LI -LI 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0473] Embodiment L20. The method of any one of embodiments LI -LI 9, wherein the regimen of administration of the chlorite salt lasts at least six months.

[0474] Embodiment L21 . The method of any one of embodiments LI -LI 9, wherein the regimen of administration of the chlorite salt lasts at least twelve months.

[0475] Embodiment L22. The method of any one of embodiments LI -LI 9, wherein the regimen of administration of the chlorite salt lasts at least twenty -four months.

[0476] Embodiment L23. The method of any one of embodiments LI -LI 9, wherein the regimen of administration of the chlorite salt lasts until death of the subject.

[0477] Embodiment L24. The method of any one of embodiments L1 -L23, wherein the regimen of administration of the chlorite salt is about 0.2 mg / kg / day to about 3.5 mg / kg / day.

[0478] Embodiment Ml . A method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma sCD163 level of the subject based on a blood assay; c) subsequent to the obtaining the first plasma sCD163 level of the subject, obtaining a second plasma sCD163 level of the subject based on a blood assay; d) determining that the second plasma sCD 163 level of the subject is a decrease of at least ten percent in comparison to the first plasma sCD163 level of the subject; and e) based at least in part on the determining that the second plasma sCD 163 level of the subject is a decrease of at least ten percent in comparison to the first plasma sCD163 level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.WSGR Docket No. 59077-714.601

[0479] Embodiment M2. The method of embodiment Ml, wherein the blood assay is a quantification of sCD163 levels in blood of the subject by high performance liquid chromatography.

[0480] Embodiment M3. The method of any one of embodiments Ml -M2, wherein the obtaining the first plasma sCD163 level of the subject based on the blood assay comprises performing the blood assay; and the obtaining the second plasma sCD163 level of the subject based on the blood assay comprises performing the blood assay.

[0481] Embodiment M4. The method of any one of embodiments Ml -M3, wherein the chlorite salt is sodium chlorite.

[0482] Embodiment M5. The method of any one of embodiments Ml -M4, wherein the regimen of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient.

[0483] Embodiment M6. The method of embodiment M5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0484] Embodiment M7. The method of any one of embodiments M5-M6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0485] Embodiment M8. The method of any one of embodiments M5-M7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0486] Embodiment M9. The method of any one of embodiments M5-M8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0487] Embodiment M10. The method of any one of embodiments M5-M9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0488] Embodiment Ml 1. The method of any one of embodiments Ml -M10, wherein the administration is oral.

[0489] Embodiment Ml 2. The method of any one of embodiments Ml -Ml 1, wherein the administration is parenteral.

[0490] Embodiment Ml 3. The method of any one of embodiments Ml -Ml 2, wherein the administration of the chlorite salt is by infusion over about 30 to about 60 minutes.

[0491] Embodiment M14. The method of any one of embodiments Ml -M13, wherein the administration of the chlorite salt is by infusion over about 30 minutes.

[0492] Embodiment Ml 5. The method of any one of embodiments Ml -Ml 4, wherein the administration of the chlorite salt is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.WSGR Docket No. 59077-714.601

[0493] Embodiment Ml 6. The method of any one of embodiments Ml -Ml 5, wherein the administration of the chlorite salt occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

[0494] Embodiment Ml 7. The method of any one of embodiments Ml -Ml 5, wherein the administration of the chlorite salt occurs about every other day.

[0495] Embodiment Ml 8. The method of any one of embodiments Ml -Ml 5, wherein the administration of the chlorite salt occurs about every day.

[0496] Embodiment Ml 9. The method of any one of embodiments Ml -Ml 8, wherein the subject had taken riluzole prior to beginning the regimen.

[0497] Embodiment M20. The method of any one of embodiments Ml -Ml 9, wherein the regimen of administration of the chlorite salt lasts at least six months.

[0498] Embodiment M21. The method of any one of embodiments Ml -Ml 9, wherein the regimen of administration of the chlorite salt lasts at least twelve months.

[0499] Embodiment M22. The method of any one of embodiments Ml -Ml 9, wherein the regimen of administration of the chlorite salt lasts at least twenty -four months.

[0500] Embodiment M23. The method of any one of embodiments Ml -Ml 9, wherein the regimen of administration of the chlorite salt lasts until death of the subject.

[0501] Embodiment M24. The method of any one of embodiments Ml -M23, wherein the regimen of administration of the chlorite salt is about 0.2 mg / kg / day to about 3.5 mg / kg / day.

[0502] Embodiment N1. A method comprising: a) starting a subject who has amyotrophic lateral sclerosis on a regimen of administration of a chlorite salt that is therapeutically effective for amyotrophic lateral sclerosis; b) obtaining a first plasma LPS level of the subject based on a blood assay; c) sub sequent to the obtaining the first plasma LPS level of the subject, obtaining a second plasma LPS level of the subject based on a blood assay; d) determining that the second plasma LPS level of the subject is a decrease of at least ten percent in comparison to the first plasma LPS level of the subject; and e) based at least in part on the determining that the second plasma LPS level of the subject is a decrease of at least ten percent in comparison to the first plasma LPS level of the subject, recommending that the subject continue the regimen of administration of the chlorite salt.

[0503] Embodiment N2. The method of embodiment Nl, wherein the blood assay is a quantification of LPS levels in blood of the subject by high performance liquid chromatography.

[0504] Embodiment N3. The method of any one of embodiments N 1 -N2, wherein the obtaining the first plasma LPS level of the subject based on the blood assay comprisesWSGR Docket No. 59077-714.601 performing the blood assay; and the obtaining the second plasma LPS level of the subject based on the blood assay comprises performing the blood assay.

[0505] EmbodimentN4. The method of any one of embodiments N1 -N3, wherein the chlorite salt is sodium chlorite.

[0506] EmbodimentN5. The method of any one of embodiments N 1 -N4, wherein the regimen of the chlorite salt comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient.

[0507] Embodiment N6. The method of embodiment N5, wherein the pharmaceutical formulation has a pH from 7.5 to 9.5.

[0508] Embodiment N7. The method of any one of embodiments N5 -N6, wherein the pharmaceutically -acceptable excipient is dibasic sodium phosphate.

[0509] Embodiment N8. The method of any one of embodiments N5 -N7, wherein the pharmaceutical formulation is substantially free of preservatives.

[0510] EmbodimentN9. The method of any one of embodiments N5-N8, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

[0511] Embodiment N10. The method of any one of embodiments N5 -N9, wherein the pharmaceutical formulation has a volume of about 250 m .

[0512] Embodiment N11 . The method of any one of embodiments N1 -N10, wherein the administration is oral.

[0513] Embodiment N12. The method of any one of embodiments N1 -N11, wherein the administration is parenteral.

[0514] Embodiment N13. The method of any one of embodiments N1 -N 12, wherein the administration of the chlorite salt is by infusion over about 30 to about 60 minutes.

[0515] Embodiment N14. The method of any one of embodiments N1 -N13, wherein the administration of the chlorite salt is by infusion over about 30 minutes.

[0516] Embodiment N15. The method of any one of embodiments N1 -N 14, wherein the administration of the chlorite salt is of about 2 mg / kg subject body mass of the chlorite salt based on chlorite ion.

[0517] Embodiment N16. The method of any one of embodiments N1 -N15, wherein the administration of the chlorite salt occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regim en.

[0518] Embodiment N17. The method of any one of embodiments N1 -N15, wherein the administration of the chlorite salt occurs about every other day.WSGR Docket No. 59077-714.601

[0519] Embodiment N18. The method of any one of embodiments N1 -N15, wherein the administration of the chlorite salt occurs about every day.

[0520] Embodiment N19. The method of any one of embodiments N1 -N18, wherein the subject had taken riluzole prior to beginning the regimen.

[0521] Embodiment N20. The method of any one of embodiments N1 -N19, wherein the regimen of administration of the chlorite salt lasts at least six months.

[0522] Embodiment N21 . The method of any one of embodiments N1 -N19, wherein the regimen of administration of the chlorite salt lasts at least twelve months.

[0523] Embodiment N22. The method of any one of embodiments N1 -N19, wherein the regimen of administration of the chlorite salt lasts at least twenty -four months.

[0524] Embodiment N23. The method of any one of embodiments N1 -N 19, wherein the regimen of administration of the chlorite salt lasts until death of the subject.

[0525] Embodiment N24. The method of any one of embodiments N1 -N23, wherein the regimen of administration of the chlorite salt is about 0.2 mg / kg / day to about 3.5 mg / kg / dayEXAMPLESExample 1: Survival Study

[0526] Purpose: To determine the overall survival benefit of 2 mg / kg of sodium chlorite (based on mass of chlorite ion) in a protocol-defined prespecified analysis of retrospective survival data of subjects with amyotrophic lateral sclerosis (ALS) who participated in two placebo-controlled phase 2 clinical trials.

[0527] Methods: Survival data were collected for 269 of 274 subjects with ALS who participated in two phase 2 placebo-controlled clinical trials of sodium chlorite and who received 6 cycles of treatment over a 6 months’ period. Overall survival (OS) was defined as: the time from the original random assignment to the date of death due to any cause (event); or, for subjects for whom no date of death was discernable at the end of the study follow-up period, the date of censoring was the last date the subject was known to be alive (in the intention -to-treat population) or the end of the study follow-up period whichever occurred first, was analyzed in the intention-to-treat population. Kaplan-Meier methods were used to estimate survival probabilities and curves.

[0528] Results: For the primary' endpoint, the median OS for the overall population over the entire follow-up duration was 2.7years (95% CI: 2.4, 3.5) for the 2 mg / kg group, and 2.3 yearsWSGR Docket No. 59077-714.601(95% CI: 1.8, 2.9) for the placebo group, representing a 4.8 months’ advantage for the sodium chlorite recipients (p=0.060). The hazard ratio (HR) was 0.76 (95% CI: 0.57, 1.02) . For the prespecified secondary endpoint of OS among those aged <65 years, the median OS was 3.3 years (95% CI: 2.4, 3.9) in the 2 mg / kg group, and 2.4 years (95% CI: 1.7, 3.3) in the placebo group, representing a 10.8 months’ advantage for the sodium chlorite recipients (p=022). The associated HR was 0.68 (95% CI: 0.49, 0.9).

[0529] € Conclusion: The study findings report that just a 6 months’ treatment course of 2 mg / kg resulted in a clinically meaningful effect on the rate of disease progression as measured by OS.

[0530] The intent of the study was to ascertain whether positive impact on slowing the rate of decline in vital capacity in the post hoc analyses of pooled data from two phase 2 clinical studies of sodium chlorite translated to an effect on overall survival assessed through the collection of these new data given that respiratory failure is a major factor contributing to death in subjects with ALS.

[0531] Study Patients: This study was designed to collect survival data for 274 subjects with El Escorial criteria category probably / definite who previously participated in two phase 2 clinical studies of sodium chlorite. The phase 2 clinical studies were: (a) enrolling 136 subjects randomized to receive either: 1 mg / kg of (n=49); 2 mg / kg (n=45); or normal saline as placebo (n=42); and, (b) enrolling 138 subjects randomized to receive either: 2 mg / kg (n=70), or normal saline as placebo (n=68).

[0532] In both studies, all subjects were enrolled within 3 years of symptom onset and vital capacity was >80% forced vital capacity (FVC) for phase 2a and >70% slow vital capacity (SVC) for phase 2b. FVC and SVC are highly correlated and both FVC and SVC measurements and loss thereof over time relate to the quality of life and mortality in ALS subjects. All subjects enrolled in the phase 2b study were required to have a plasma high-sensitivity C-reactive protein (hs-CRP) concentration of> 0.113 mg / dL at the pre-screening visit. Each subject was planned to receive six (6) dosing schedules of the applicable study drug over a 6 months’ treatment period. Demographic data (i.e., age, sex, race, ethnicity) were taken from the data already collected for those original clinical studies.

[0533] Study design and data collection: This study was a retrospective study. Survival status data and subject dates of deaths were identified using publicly available records and databases, such as the Social Security Death Index, State death indices, and obituary resources. Where such data were not available, a review of survival status data from medical records of the treating institutions’ subject charts was performed where permissible to identify missing dates of death or last known date alive, which included a review of the primary record to determine complianceWSGR Docket No. 59077-714.601 to protocol requirements; review of the primary record to determine that adequate source documentation was available to support reported data; and, review of data collection forms to determine accurate reporting of research data. Sites were asked to provide information about subject survival status, date of death, and cause of death, if known. For the purposes of this study, the longest follow-up sought to determine survival status was 11 years and 8 months. Data collection occurred over about one year.

[0534] Study end points: The primary end point was the determination of overall survival in all subjects who received at least one infusion of sodium chlorite at a dose of 2 mg / kg compared with placebo. The secondary endpoints were: the determination of overall survival in all subjects aged <65 years who received at least one infusion of sodium chlorite at a dose of 2 mg / kg compared with placebo; and, determination of overall survival in all subjects who were originally enrolled in the Phase 2a study and received at least one infusion of sodium chlorite at a dose of 1 mg / kg compared with the original study -matched concurrently randomized placebo.

[0535] Statistical analysis: The overall analysis population (i.e., ITT population) was defined as all subjects with ALS who were enrolled in this study and had previously received a dose of sodium chlorite or placebo. The primary analysis population was defined as all subjects who received a dose of 2 mg / kg or placebo and were enrolled in this study. The secondary analysis population was defined as all subjects who received sodium chlorite at a dose of 1 mg / kg or matched, concurrently randomized placebo and were enrolled in this study.

[0536] The analysis outcome was overall survival, which was defined as the time from the original random assignment to the date of death due to any cause (event). For subjects for whom no date of death was discernable at the end of the study follow-up period, the date of censoring was the last date the subject was known to be alive (in the intention -to-treat population) or the end of the study follow-up period, whichever occurred first. Overall survival was censored for subjects at the date of randomization if randomized but had no follow-up.

[0537] Patient demographics / characteristics data from the clinical studies were merged with the collected survival data at the time of analyses. The original study subject ID number and group assignment were collected to merge the datasets appropriately. In the case of discrepant data between the current study CRF data and original clinical study data, the original clinical study data were considered the primary data source .

[0538] Data from the original phase 2 clinical studies had been unblinded. Thus, before data from the current study were shared with the study team, variables (i.e., group assignment) were blinded by a data analyst outside the study team. All study -level analyses were performed blinded. The study team only was unblinded after final study -level results were produced. To make appropriate group comparisons across studies, the data analyst on the study team becameWSGR Docket No. 59077-714.601 unblinded after study -level results were finalized and then proceeded with the integrated analysis across the two clinical studies.

[0539] For descriptive subject characteristics, continuous data were described by mean, standard deviation (SD), median, interquartile range (including first and third quartiles), minimum, maximum, and number of known and number of unknown (missing) observations. Categorical variables were described by frequency and percentages (n, %). Percentages were calculated using the specified denominator in TABLE 2.

[0540] Kaplan-Meier methods were used to estimate survival probabilities and curves. For the comparison of the 2 mg / kg vs placebo groups, the stratified log-rank statistic was used as the primary analysis to assess differences in overall survival between the treatment and placebo groups forthe ITT population, where stratification was by the original study, (i.e., phase 2a vs phase 2b). Forthe comparison of the 1 mg / kg vs placebo groups, since data were only from the phase 2a study, the log-rank statistic without stratification by study was used. Supportive analyses forthe comparison of 2 mg / kg vs placebo groups included separate analyses by study using the log-rank statistic.

[0541] For each outcome analysis, the number and percentage of subjects with the event, the number and percentage of subjects censored, and Kaplan -Meier estimates of the quartiles of the survival distribution along with corresponding 95% confidence intervals were calculated.Regarding additional descriptive analyses, the hazard ratio and corresponding 95% confidence interval comparing sodium chlorite to placebo were estimated using Cox proportional -hazards model, stratified by the original study (phase 2a, phase 2b). Descriptive assessments were performed regarding the assumption of proportionality of hazard ratios and influential observations were assessed. All p-values were two-sided. The analyses using the stratified Cox proportional hazards model were based on the Wald statistic from the Cox partial likelihood and were descriptive only, in contrast to the previously -specified primary analyses based on the stratified log-rank statistic, based on the Score statistic from the Cox partial likelihood. All time- to-event analyses were reported in years. The random assignment date was ascertained from the original study data. Kaplan-Meier estimates were shown over time post randomization, and tabulated for one year, two years, three years, four years, five years, and 10 years. The duration of one year was considered as 365.25 days.

[0542] Results: Of the combined 274 subjects originally randomized in the Phase 2 studies, date of death or last known date alive could be discerned for 269 (98.2%). With respect to the five subjects for whom no data could be found: two were from one US site where the sponsor had randomization codes for two, but the relevant site had no subject identifiers forthose codes; and of the remaining three, all from one other US site, subject identifiers existed, but noWSGR Docket No. 59077-714.601 outcomes data could be identified due to missing subject records.

[0543] Baseline characteristics of subjects: Baseline characteristics for the sodium chlorite and placebo recipients for each of the two original studies are presented in TABLE 2. Due to when the original studies were performed, no information on genetic mutations associated with ALS disease progression was available.

[0544] Across both studies, the overall median age at time of randomization was 57 years old, and the interquartile range spanned 48 to 63 years old. The majority of subjects were male (69.0%), non-Hispanic or Latino (94.5%), and white (94.2%). Most subjects (90.9%) had sporadic ALS with site of ALS onset in the limbs (84.7%). Overall, the median duration of ALS symptom onset was 18.3 months The majority of subjects across both studies had prior riluzole use (75.5%) and were concurrent riluzole users (69.3%) at the time of their enrollment in the original studies.

[0545] Overall survival in subjects receiving 2 mg / kg chlorite vs. placebo: OS among subjects who received sodium chlorite at a dose of 2 mg / kg compared to placebo was assessed with respect to the overall population (FIG. 3) and those <65 years old (FIG. 4). In the overall population, the median survival (95% confidence interval [CI]) over the entire follow-up duration was 2.7 years (95% CI: 2.4, 3.5) and 2.3 years (95% CI: 1.8, 2.9) in the 2 mg / kg and placebo groups respectively (p=0.060). The associated hazard ratio (HR) was 0.76 (95% CI: 0.57, 1.02).

[0546] Among those aged <65 years, the median survival (95% CI) was 3.3 years (95% CI: 2.4, 3.9) in the 2 mg / kg group and 2.4 years (95% CI: 1.7, 3.3) in the placebo group, representing a 10.8 months’ advantage for the sodium chlorite recipients (p=0.022). The associated HR was 0.68 (95% CI: 0.49, 0.9). The difference in proportion of subjects alive for the 2 mg / kg group compared placebo group between one and 10 years after randomization ranged from 3.9% (year 1) to 13.9% (year 4).

[0547] Amongthe <65-year-old subpopulation, survival probabilities between the 2 mg / kg and placebo groups were compared post-hoc at shorter follow-up intervals. The median survival (95% CI) over four- and five-year follow-up periods was each 3.3 years (95% CI: 2.4, 3.9) in the 2 mg / kg group and 2.4 years (95% CI: 1.7, 3.3) in the placebo group (p=0.038 and p=0.027 respectively).

[0548] Overall survival in subjects receiving 1 mg / kg sodium chlorite vs. placebo: OS among subjects who received sodium chlorite at a dose of 1 mg / kg compared to placebo was also assessed among the overall population. The median survival (95% CI) over the entire follow-up duration was 2.2 years (95% CI: 1.7, 3.4) in the 1 mg / kg group and 2.1 years (95% CI: 1.6, 3.4) in the placebo group (FIG. 5). The associated HR was 0.91 (95% CI: 0.58, 1.42).WSGR Docket No. 59077-714.601

[0549] Limitations: This study collected survival data from subjects who were enrolled in two phase 2 clinical studies. Survival status was determined and confirmed through research of publicly available records and databases; and in cases where data were not available, through review of subject medical records. The length of time that elapsed since the closure of these studies contributed to the challenges in data collection, for example, departures of the original investigator and / or site staff from the sites, and the limited number of site staff to retrieve and provide the required data. However, given that the data collection form required a minimum amount of data be collected, the impact on data quality was assumed to be minimal. Furthermore, OS is well established as an objectively measured, unambiguous, clinically significant outcome — unaffected by the timing of assessment, and not subject to the potential investigator biases associated with outcomes that require clinical judgment. In both phase 2 studies, the majority of subjects in both treatment and placebo cohorts received concurrent riluzole, and survival outcomes in the current study did not adjust for the potential effect of riluzole on survival probabilities.

[0550] Discussion: In this analysis of survival encompassing subjects randomized in the two original phase 2 studies of sodium chlorite, those subjects randomized to receive a 6 months’ treatment course of sodium chlorite at a dose of 2 mg / kg had a median OS for the predefined primary endpoint that was 4.8 months longer than that of the group randomized to receive placebo. In the predefined secondary endpoint, those subjects aged 65 years or less and randomized to receive a 6 months’ treatment course of sodium chlorite at a dose of 2 mg / kg, had a median OS that was 10.8 months longer than that of the group randomized to receive placebo. The absence of an observable benefit in those subjects receiving sodium chlorite at the lower dose of 1 mg / kg supports the conclusion that the effect at the higher dose of 2mg / / kg is a clinically meaningful treatment effect. Furthermore, when taken in the broader context of reported analyses of the effect of sodium chlorite on vital capacity, ALSFRS-R total score and inflammatory biomarkers, these analyses of newly collected survival data not just add to the totality of the evidence of a positive treatment effect of sodium chlorite in ALS but are confirmatory of a therapeutic benefit of sodium chlorite in extending life.

[0551] FIG. 6 illustrates the effectiveness of sodium chlorite with respect to disease progression in the total randomized population compared with those aged 65 years or less appears to be driven by those subjects aged over 65 years at the time of commencement of treatment. Older subjects are susceptible to a higher progression rate and a shorter duration of survival.

[0552] The new survival data collected in this study were analyzed by an intention -to-treat ITT methodology. The application of an ITT analysis results is a more conservative estimate ofWSGR Docket No. 59077-714.601 treatment effect, because ITT includes all subjects in the groups to which the subjects were randomly assigned, regardless compliance with inclusion or exclusion criteria or the treatment actually received, and irrespective of subsequent withdrawal from treatment or deviation from the protocol. ITT ignores noncompliance, protocol deviations, withdrawal, and anything that happens after randomization and avoids overoptimistic estimates of the efficacy of an intervention resulting from the removal of non-compliers by accepting that noncompliance and protocol deviations are likely to occur in actual clinical practice. In this instance, the application of the ITT analysis accepts the real-world nature of clinical practice and the anticipated treatment effect of sodium chlorite irrespective of alternative treatments, therapeutic agents, or permanent, assisted ventilation.

[0553] In conclusion, the findings reported here indicate that just a 6 months’ treatment course of sodium chlorite resulted in a clinically meaningful effect on the rate of disease progression as measured by overall survival, an objectively measured, unambiguous, clinically -significant outcome unaffected by assessment timing, and not prone to the potential investigator biases associated with endpoints that require clinical judgment, and that the magnitude of that effect was greatest in those subjects aged 65 years or younger.TABLE 2.WSGR Docket No. 59077-714.601WSGR Docket No. 59077-714.601Example 2: Creatinine Study

[0554] Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive uniformly fatal disease that makes development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Clinical studies with NP001 , an intravenously administered form of the innate immune system regulator NaC102, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. This example presents pooled analysis of all subjects who received at least one dose of drug in two six-month NPOOl trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated subjects who compared to placebo had up to a year of extended survival. The observed longer survival in ALS subjects with the greatest inflammation associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and thatNPOOl is a disease modifying drug with sustained clinical activity.

[0555] Treatment targeting the innate immune dysfunction of ALS by NP001 can be assessed quantitatively by evaluation of creatinine and VC changes from baseline. These changes are related to overall survival (OS) for ALS subjects. FIG. 13A-C illustrates this theory of ALS pathogenesis as being an immune activation disorder with ALS initiation at the neuromuscular junction (NMJ) driving the pathogenesis of disease. To test this hypothesis, we used data collected from subjects with ALS who participated in two six -month studies of NP001.

[0556] FIG. 13A-C illustrates innate immune destruction of the neuromuscular junction (NMJ) leading to loss of muscle, respiratory function and death. A) The motor neuron axon outgrowths interact with the muscle at the neuromuscular junction (NMJ). This is the site where inappropriately processed disease-associated proteins such as TDP43 are recognized by the innate immune system and begin the process of motor neuron and muscular dysfunction. B) Loss of NMJ function leads to muscle loss. In addition, the acute phase reaction consumes muscle as a source of rare amino acids such as phenylalanine, tryptophan, and tyrosine turning normal muscle into a wasted sarcopenic muscle. Blood creatinine levels quantify the muscle as a source of APP amino acids and CRP levels increase. C) The diaphragm is innervated by theWSGR Docket No. 59077-714.601 phrenic nerve, an outgrowth of a lower motor neuron. VC measurements indirectly measure the function of the NMJ.

[0557] Two trials were conducted as placebo-controlled 6 month studies. No drug-related Serious Adverse Events (SAEs) occurred in either trial. All subjects studied here were treated with either 2 mg / kg chlorite of NP001 orplacebo. FIG. 7 provides a high level summary of the Phase 2A trial.

[0558] In both studies, all subjects were enrolled within 3 years of symptom onset. The additional criteria for all subjects enrolled in one study included a plasma high -sensitivity C- reactive protein (hs-CRP) concentration of > 1.13 mg / L at the pre-screening visit. For each trial, subjects were planned to receive a total of 20 infusions administered intravenously over 6 cycles during a 6-month study with 4 weeks between the start of each cycle. Cycle 1 consisted of 30- minute infusions over 5 consecutive days. Cycles 2, 3, 4, 5, and 6 each consisted of 3 consecutive 30-minute daily infusions.

[0559] The study focused on the percentage change in predicted vital capacity (VC) over the six-month studies. One trial assessed the predicted VC in FVC whereas the other assessed predicted VC in SVC. Since predicted VC values between FVC and SVC are comparable, the evaluation of NP001 effects on VC combined changes from both trials normalized to % VC change from baseline [100 x (predicted VC at study end - predicted VC at baselinej / predicted VC at baseline],

[0560] Analyses presented here are limited to the completers, defined as all subjects who received NP001 at a dose of 2 mg / kg or placebo and had completed the 6 -cycle treatments with ALSFRS-R total score assessment at the end of the study, resulting in a total of 189 participants, 91 of NP001 2 mg / kg chlorite and 98 of placebo, analyzed.

[0561] The serum levels of creatinine as safety biomarkers were collected at baseline / pre- screening in both trials and grouped for analyses based on clinical threshold levels. Given sex differences in muscle mass, baseline creatinine was further categorized by accounting for sex. FIG. 8 shows a summary of baseline creatinine levels in the subjects. 42% of subjects were observed to have serum creatinine levels less than the normal range of 60 pM / L. The participants with serum creatinine atbaseline for males < 71 pM / L or females < 53 pM / L were defined as the low creatinine group and the high creatinine group included those with serum creatinine > 71 pM / L for males or > 53 pM / L for females at baseline.

[0562] The effect of sodium chlorite treatment was assessed in the intention -to-tre at population on creatinine loss. FIGs. 9 and 10 show changes in creatinine levels from baseline for sodium chlorite (NPOOl)-treated and placebo-treated subjects over the 6-month treatment period. NP001 was observed to arrest creatinine loss compared to placebo.WSGR Docket No. 59077-714.601

[0563] FIG. 11 shows the change in vital capacity following treatment with NP001 in subjects under 65 years of age with baseline serum creatinine < 60 pM / L. NP001 treatment preserved vital capacity in subjects with baseline serum creatinine < 60 pM / L and did not have an effect in subjects with baseline serum creatinine > 60 pM / L.

[0564] Survival data for ALS subjects in the intention-to-treat (ITT) population were collected. Overall survival (OS) was defined as the time in months from date of randomization to date of death due to any cause, or to last contact / known alive for subjects lost to follow-up.

[0565] Statistical analysis was performed using IMP Pro 17 (SAS Institute, Cary, North Carolina) and SAS 9.4 (SAS Institute, Cary, North Carolina) and packages surv and survminer in R. Data were summarized as counts and percentages for categorical data and using standard univariate descriptive statistics (number of participants, mean, standard deviation, median) for continuous / discrete data by treatment group. Preliminary analyses of categorical data were analyzed using Fisher’s exact test and Chi-square tests, and of continuous / discrete data using t- tests or Wilcoxon rank sum tests as appropriate.

[0566] Overall survival differences by treatment / group were assessed using a log-rank test. Kaplan-Meier methods were used to estimate survival probabilities and curves. Cox- proportional hazards models were used to estimate the hazard ratio associated with dying for subjects treated with NP001 compared with those given placebo. The assumption of proportionality of hazards overtime were assessed using the Schoenfeld test. Patients who were lost to follow-up or alive at the end of the follow-up period were considered censored in all survival analyses. All statistical tests were two-sided and considered statistically significant for p-value < 0.05. FIG. 12 shows a Kaplan-Meier curve of survival probability for Phase 2A subjects with baseline serum creatinine < 60 pM / L. Sodium chlorite treatment (NP001) extended survival by 12 months compared to placebo.

[0567] Patient demographics and disease characteristics did not differ by treatment groups in the completers with the exception of a lower percentage of subjects with familial ALS (96.7% sporadic) in the NP001 treatment group compared to the placebo group (82.7% sporadic).

[0568] When familial subjects were removed from any analysis, the outcomes of all group analyses were not statistically different. For the current study, survival analysis was performed on completers who had inflammation as documented by having a plasma hs -CRP level > 1.13 mg / L at baseline. Considering the disproportion in ALS subtype had many more familial cases assigned to placebo, placebos with and without familial subjects included had survival curves indistinguishable one from another.

[0569] TABLE 3 shows subject demographics and disease characteristics of completers with plasma CRP > 1.13 mg / L at baseline.WSGR Docket No. 59077-714.601TABLE 3 Baseline demographics and characteristics of phase 2A and 2B completers1with plasma CRP > 1.13 mg / L at baseline.Abbreviation: n, number of participants. NS, not significant. SD, standard deviation.1Completers, the participants who had completed the 6 -cycle treatments and had ALSFRS-R total score assessment at the end of study.2Months from ALS symptom onset to baseline.

[0570] In the completers, the median OS was 38.6 months and 28.4 months in the 2 mg / kgNP001 and placebogroups, respectively (log-rank, p = 0.04). Patients treated with NP001 had aWSGR Docket No. 59077-714.601 better survival outcome than did those on placebo [hazard ratio (HR) = 0.72, 95% CI: 0.52, 0.99], as shown in FIG. 14.

[0571] In completers with plasma CRP > 1.13 mg / L at baseline, NP001 treatment was statistically significantly associated with survival duration. Median survival was 42.8 months and 28.4 months in the 2 mg / kgNPOOl and placebo groups, respectively (FIG. 15, log-rank, p = 0.002; HR = 0.57, 95% CI: 0.39, 0.82 for NPOOl vs placebo group).

[0572] FIG. 16 shows the % VC change from baseline of the NP001 treatment arm vs. placebo group in completers with plasma CRP > 1.13mg / L at baseline. The NP001 treatment arm lost 29% less respiratory function than the placebo arm by the end of the study (NP001 = - 9.1% vs. Placebo = - 12.9%) (Wilcoxon, p = 0.02).

[0573] NP001 efficacy defined by survival analysis and % VC change in completers. FIG. 14 shows a Kaplan-Meier curve of survival probability for subjects who received NP001 at a dose of 2 mg / kg compared with placebo in completers. In the completers, the median survival (95% confidence interval [CI]) over the entire follow-up duration was 38.6 months (95% CI: 29.9, 47.8) and 28.4 months (95% CI: 25.4, 40.0) in the 2 mg / kg NPOOl and placebo group, respectively (log-rank, p =0.04). Patients treated with NP001 hadbetter survival than did those on placebo: hazard ratio (HR) = 0.72 (95% CI: 0.52, 0.99). FIG. 15 shows a Kaplan-Meier curve of survival probability for subjects who received NP001 at a dose of 2 mg / kg compared with placebo in completers with CRP > 1.13 mg / L at baseline. In the completers with baseline CRP > 1.13 mg / L, the median survival (95% confidence interval [CI]) over the entire follow-up duration was 42.7 months (95% CL 31.3, 50.9) and 28.4 months (95% CL 24.4, 40.0) in the 2 mg / kgNPOOl and placebo group, respectively (log-rank, p = 0.002). Patients treated with NP001 had a significant benefit of survival than did those on placebo: hazard ratio (HR) = 0.57 (95% CL 0.39, 0.82). FIG. 16 shows a change in % of VC from baseline over 6 months in participants on NP001 compared with placebo in completers with high CRP at baseline.Percentage VC change from baseline for participants treated with NP001 (n = 72) is compared with the placebo group (n = 83). Bars represent mean of % VC change from baseline ± SEM. Average %VC lost over the 6 months of study: NP001 : -9.1% (-1.5% per month); Placebo: - 12.9% (-2.2% per month). The NP001 treatment arm lost 29% less respiratory function than the placebo arm by the end of the study (Wilcoxon test, p = 0.02).

[0574] FIG. 17 shows the baseline creatinine distributions in the low and high creatinine groups in completers with baseline plasma CRP > 1.13 mg / L. The median serum creatinine level was statistically significantly different between the groups (53 pM / L vs. 71 pM / L in low vs. high groups, respectively; Wilcoxon, p < 0.0001).

[0575] FIG. 17 shows Box and Whisker plots depicting the distribution of baseline serumWSGR Docket No. 59077-714.601 creatinine values for the low creatinine group (baseline creatinine < 71 pM / L for males or < 53 pM / L for females) (n = 57) and the high creatini...

Claims

WSGR Docket No. 59077-714.601CLAIMSWHAT IS CLAIMED IS:

1. A method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically - effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous person who differs from the subject only in that the analogous person does not receive the therapeutically - effective regimen of the chlorite salt.

2. The method of claim 1, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

3. The method of claim 1, wherein the chlorite salt is sodium chlorite.

4. The method of claim 1, wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient.

5. The method of claim 4, wherein the pharmaceutical formulation has a pH from 7.0 to 10.0.

6. The method of claim 4, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.

7. The method of claim 4, wherein the pharmaceutical formulation is substantially free of preservatives.

8. The method of claim 4, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

9. The method of claim 4, wherein the pharmaceutical formulation has a volume of about 250 mL.

10. The method of claim 4, wherein the administration is oral.WSGR Docket No. 59077-714.60111. The method of claim 4, wherein the administration is parenteral.

12. The method of claim 4, wherein the administration is by infusion over about 30 to about 60 minutes.

13. The method of claim 4, wherein the administration is by infusion over about 30 minutes.

14. The method of claim 4, wherein the administration is of about 2 mg chlorite ion per kg subject body mass.

15. The method of claim 4, wherein the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

16. The method of claim 1, wherein the subject had taken tofersen prior to beginning the regimen.

17. The method of claim 1, wherein the subject had taken edaravone prior to beginning the regimen.

18. The method of claim 1, wherein the subject had taken riluzole prior to beginning the regimen.

19. The method of claim 1, wherein the therapeutically-effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of the analogous, hypothetical person who differs from the subject only in that the analogous, hypothetical person does not receive the therapeutically-effective regimen of the chlorite salt by at least about 4.8 months.

20. A method of increasing term of life of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically- effective regimen of a chlorite salt, wherein the therapeutically -effective regimen of the chlorite salt increases the term of life of the subject in comparison to that of an analogous person who differs from the subject only in that the analogous person does not receive the therapeutically - effective regimen of the chlorite salt by at least about 4.8 months,WSGR Docket No. 59077-714.601 wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.0 to 10.0; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administration is by infusion over about 30 to about 60 minutes; wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass; and wherein the chlorite salt is sodium chlorite.21 . A method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically-effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous person who differs from the subject only in that the analogous person does not receive the therapeutically-effective regimen of the chlorite salt.

22. The method of claim 21, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

23. The method of claim 21, wherein the chlorite salt is sodium chlorite.

24. The method of claim 21, wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient.

25. The method of claim 24, wherein the pharmaceutical formulation has a pH from 7. 0 to 10.0.

26. The method of claim 24, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.WSGR Docket No. 59077-714.60127. The method of claim 24, wherein the pharmaceutical formulation is substantially free of preservatives.

28. The method of claim 24, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

29. The method of claim 24, wherein the pharmaceutical formulation has a volume of about 250 mL.

30. The method of claim 24, wherein the administration is oral.

31. The method of claim 24, wherein the administration is parenteral.

32. The method of claim 24, wherein the administration is by infusion over about 30 to about 60 minutes.

33. The method of claim 24, wherein the administration is by infusion over about 30 minutes.

34. The method of claim 24, wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass.

35. The method of claim 24, wherein the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

36. The method of claim 21, wherein the subject had taken tofersen prior to beginning the regimen.

37. The method of claim 21, wherein the subject had taken edaravone prior to beginning the regimen.

38. The method of claim 21, wherein the subject had taken riluzole prior to beginning the regimen.WSGR Docket No. 59077-714.60139. The method of claim 24, wherein the therapeutically -effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of the analogous person who differs from the subject only in that the analogous person does not receive the therapeutically-effective regimen of the chlorite salt by at least 0.05.

40. A method of increasing survival probability of a subject in need of treatment for amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically-effective regimen of the chlorite salt increases the survival probability of the subject in comparison to that of an analogous person who differs from the subject only in that the analogous person does not receive the therapeutically-effective regimen of the chlorite salt by at least 0.05, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.0 to 10.0; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administration is by infusion over about 30 to about 60 minutes; wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass; and wherein the chlorite salt is sodium chlorite.41 . A method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically-effective regimen of a chlorite salt, wherein the therapeutically-effective regimen comprises a course of administrations of the chlorite salt spanning at least a year.

42. The method of claim 41, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

43. The method of claim 41, wherein the chlorite salt is sodium chlorite.

44. The method of claim 41, wherein the regimen comprises administration of aWSGR Docket No. 59077-714.601 pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient.

45. The method of claim 44, wherein the pharmaceutical formulation has a pH from 7.0 to 10.0.

46. The method of claim 44, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.

47. The method of claim 44, wherein the pharmaceutical formulation is substantially free of preservatives.

48. The method of claim 44, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

49. The method of claim 44, wherein the pharmaceutical formulation has a volume of about 250 mL.

50. The method of claim 44, wherein the administration is oral.

51. The method of claim 44, wherein the administration is parenteral.

52. The method of claim 44, wherein the administration is by infusion over about 30 to about 60 minutes.

53. The method of claim 44, wherein the administration is by infusion over about 30 minutes.

54. The method of claim 44, wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass.

55. The method of claim 44, wherein the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.WSGR Docket No. 59077-714.60156. The method of claim 41, wherein the subject had taken tofersen prior to beginning the regimen.

57. The method of claim 41, wherein the subject had taken edaravone prior to beginning the regimen.

58. The method of claim 41, wherein the subject had taken riluzole prior to beginning the regimen.

59. The method of claim 41, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least about two years.

60. A method comprising administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically -effective regimen comprises a course of administrations of the chlorite salt spanning at least about a year, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.0 to 10.0; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL; wherein the administration is by infusion over about 30 to about 60 minutes; wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass; and wherein the chlorite salt is sodium chlorite.

61. A method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically-effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject.WSGR Docket No. 59077-714.60162. The method of claim 61, wherein the subject possesses a high -sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay.

63. The method of claim 61, wherein the chlorite salt is sodium chlorite.

64. The method of claim 61, wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically-acceptable excipient.

65. The method of claim 64, wherein the pharmaceutical formulation has a pH from 7.0 to 10.0.

66. The method of claim 64, wherein the pharmaceutically-acceptable excipient is dibasic sodium phosphate.

67. The method of claim 64, wherein the pharmaceutical formulation is substantially free of preservatives.

68. The method of claim 64, wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM.

69. The method of claim 64, wherein the pharmaceutical formulation has a volume of about 250 mL.

70. The method of claim 64, wherein the administration is oral.

71. The method of claim 64, wherein the administration is parenteral.

72. The method of claim 64, wherein the administration is by infusion over about 30 to about 60 minutes.

73. The method of claim 64, wherein the administration is by infusion over about 30 minutes.WSGR Docket No. 59077-714.60174. The method of claim 64, wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass.

75. The method of claim 64, wherein the administration occurs on each of five consecutive days in a first month of the regimen and on each of three consecutive days in each remaining month of the regimen.

76. The method of claim 61, wherein the subject had taken tofersen prior to beginning the regimen.

77. The method of claim 61, wherein the subject had taken edaravone prior to beginning the regimen.

78. The method of claim 61, wherein the subject had taken riluzole prior to beginning the regimen.

79. The method of claim 61, wherein the determining a vital capacity of the subject comprises spirometry.

80. A method comprising: a) administering to a subject in need of treatment for amyotrophic lateral sclerosis (ALS) a therapeutically -effective regimen of a chlorite salt, wherein the therapeutically-effective regimen comprises a course of administrations of the chlorite salt spanning six months; and b) after the six months has ended, determining a vital capacity of the subject by spirometry, wherein the subject possesses a high-sensitivity C-reactive protein (hs-CRP) level of at least 1.13 mg / L as determined by a blood assay; wherein the regimen comprises administration of a pharmaceutical formulation, wherein the pharmaceutical formulation comprises the chlorite salt and a pharmaceutically -acceptable excipient; wherein the pharmaceutical formulation has a pH from 7.0 to 10.0; wherein the chlorite salt is present in the pharmaceutical formulation at a concentration of about 62 mM; wherein the pharmaceutical formulation has a volume of about 250 mL;WSGR Docket No. 59077-714.601 wherein the administration is by infusion over about 30 to about 60 minutes; wherein the administration is of about 2 mg / kg chlorite ion per kg subject body mass and wherein the chlorite salt is sodium chlorite.

81. The method of any of claims 1-40, wherein: if a placebo-controlled study is performed on a plurality of study subjects who have ALS, wherein the study subjects were enrolled in the placebo -controlled study within three years of symptom onset of ALS, wherein: the study subjects exhibited a plasma high-sensitivity C-reactive protein (hs-CRP) concentration of > 0.113 mg / dL prior to the placebo -controlled study; about 115 of the study subjects received 2 mg / kg sodium chlorite based on chlorite ion over a period of six months on a dosing schedule of five consecutive days in a first month of the six months and on each of three consecutive days in each remaining month of the six months; about 110 of the study subjects received normal saline as placebo over a period of six months on a dosing schedule of five consecutive day sin a first month of the six months and on each of three consecutive days in each remaining month of the six months; and the placebo-controlled study estimates overall survival of the study subjects by Kaplan- Meier analysis, wherein the overall survival for a study subject is measured from a first time point to a second time point, wherein the first time point is a time at which the study subject is assigned to receive either 2 mg / kg sodium chlorite based on chlorite ion or normal saline as placebo, and the second time point is death or termination of the placebo-controlled study, whichever occurs first, then the placebo-controlled study estimates median survival of: i) 2.7 years for all study subjects receiving2 mg / kg chlorite ion per kg subjectbody mass with a 95% confidence interval of 2.4 to 3.5; ii) 2.3 years for all study subjects receiving normal saline as placebo with a 95% confidence interval of 1.8 to 2.9; iii) 3.3 years for all study subjects under age 65 receiving 2 mg / kg chlorite ion per kg subject body mass with a 95% confidence interval of 2.4 to 3.9; and iv) 2.4 years for all study subjects under age 65 receiving normal saline as placebo with a 95% confidence interval of 1.7 to 3.3.

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