Methods for Treating ALS Patients

Abstract

Provided herein are methods and compositions for the treatment of ALS using pharmaceutical compositions comprising chlorite or sodium chlorite for a target ALS patient population.Also provided herein are methods for identifying a target ALS patient population likely to be responsive to treatment with a pharmaceutical composition comprising chlorite or sodium chlorite, comprising identifying ALS patients with elevated plasma C-reactive protein (CRP) levels, and / or patients aged 40-65 years, with sporadic ALS pathology, or a combination thereof.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 252,061, filed October 4, 2021, and U.S. Provisional Patent Application No. 63 / 301,476, filed January 20, 2022, and U.S. Provisional Patent Application No. 63 / 302,000, filed January 21, 2022, each of which is incorporated by reference in its entirety and for all purposes as if fully set forth herein. [Background technology]

[0002] background Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that destroys motor neurons in the brain and spinal cord, eventually causing muscle paralysis and death, usually within 2-4 years of diagnosis. There is no cure for ALS and no effective treatment. There are two drugs approved for use in ALS patients, which can only briefly extend life or slow progression in a small proportion of very recently diagnosed patients, and most ALS patients do not have any type of effective treatment. Summary of the Invention [Means for solving the problem]

[0003] overview Although NP001, a formulation of purified sodium chlorite, has not been effective in treating all ALS patients, a portion of ALS patients treated with NP001 experience a halt or slowing of disease progression. Given that there is no effective treatment for ALS, a method to identify which ALS patients are likely to respond to NP001 could provide an effective treatment for a subpopulation of ALS patients.

[0004] In response to this need, methods are disclosed herein for identifying and treating subpopulations of ALS patients who are likely to be responsive to treatment with NP001 (purified sodium chlorite) and experience halting or slowing of disease progression upon treatment.Since there is no effective treatment for ALS, such treatments that halt or slow disease progression in subpopulations of ALS patients represent a major advance in the treatment of ALS.

[0005] In one aspect, provided herein is a method of treating amyotrophic lateral sclerosis (ALS) in a subject between 40 and 65 years of age, comprising intravenously administering to the subject a chlorite composition comprising purified sodium chlorite, the chlorite composition being administered at 2 mg chlorite per kg of the subject's body weight, the chlorite composition being administered daily for 5 consecutive days for the first month and 3 consecutive days for each subsequent month, the purified sodium chlorite being at least 97% pure, the purified sodium chlorite comprising 2.0% or less sodium chloride, the purified sodium chlorite comprising 1.0% or less sodium chlorate, the chlorite composition comprising disodium hydrogen phosphate, and having a pH between 7.5 and 9.5. The purity of the sodium chlorite may be determined by ion chromatography. The method may slow the progression of ALS in the subject, or the decline in the subject's function, or the decline in the subject's lung capacity. The chlorite composition may be administered over a period of 60 minutes. The subject may have a plasma C-reactive protein (CRP) level of at least 1.13 mg / L or at least 3.0 mg / L. The subject may have a plasma hs-CRP level of at least 1.13 mg / L or at least 3.0 mg / L. The subject may have experienced symptoms of ALS for at least 18 months prior to administering the chlorite composition to the subject, and optionally the symptoms of ALS include muscle weakness, muscle spasms, muscle contractions, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, loss of coordination, pain, fatigue, difficulty walking, increased clumsiness, or a combination of two or more of these. The subject may have sporadic ALS pathology and / or not have inherited ALS pathology.The subject may not have a mutation in an ALS-associated gene, where the mutation is in SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANX It can be in A11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD.

[0006] In a further aspect, provided herein is a method of treating amyotrophic lateral sclerosis (ALS) in a subject having a plasma C-reactive protein (CRP) level of at least 1.13 mg / kg, comprising intravenously administering to the subject a chlorite composition comprising purified sodium chlorite, the chlorite composition being administered at 2 mg chlorite per kg of the subject's body weight, the chlorite composition being administered daily for five consecutive days in a first month and three consecutive days in a subsequent month, the purified sodium chlorite being at least 97% pure, the purified sodium chlorite comprising no more than 2.0% sodium chloride, the purified sodium chlorite comprising no more than 1.0% sodium chlorate, the chlorite composition comprising disodium hydrogen phosphate, and having a pH of 7.5 to 9.5. The subject may be 40 to 65 years old. The chlorite composition may be administered over a period of 60 minutes.

[0007] In another aspect, provided herein is a method of treating amyotrophic lateral sclerosis (ALS) in a subject having a plasma hs-CRP level of at least 1.13 mg / kg, comprising intravenously administering to the subject a chlorite composition comprising purified sodium chlorite, the chlorite composition being administered at 2 mg chlorite per kg of the subject's body weight, the chlorite composition being administered daily for five consecutive days in a first month and three consecutive days in a subsequent month, the purified sodium chlorite being at least 97% pure, the purified sodium chlorite comprising no more than 2.0% sodium chloride, the purified sodium chlorite comprising no more than 1.0% sodium chlorate, the chlorite composition comprising disodium hydrogen phosphate and having a pH of 7.5-9.5. The subject may be 40-65 years old. The chlorite composition may be administered over a period of 60 minutes.

[0008] In a further aspect, provided herein is a method of treating amyotrophic lateral sclerosis (ALS) in a subject aged 60 years, comprising administering to the subject a chlorite composition comprising purified sodium chlorite intravenously over a period of 60 minutes, the chlorite composition being administered at 2 mg chlorite per kg of subject body weight, the chlorite composition being administered daily for 5 consecutive days in a first month and 3 consecutive days in a subsequent month, the purified sodium chlorite being at least 97% pure, the purified sodium chlorite comprising 2.0% or less sodium chloride, the purified sodium chlorite comprising 1.0% or less sodium chlorate, the chlorite composition comprising disodium hydrogen phosphate, and having a pH of 7.5-9.5. The purity of the sodium chlorite may be determined by ion chromatography. The subject may have a plasma hs-CRP level greater than 1.13 mg / L, and / or the subject may be aged 40-65 years.

[0009] In another aspect, a method of treating amyotrophic lateral sclerosis (ALS) in a subject comprises intravenously administering to the subject a chlorite composition comprising purified sodium chlorite, wherein the chlorite composition is administered at 2 mg chlorite per kg body weight of the subject, wherein the chlorite composition is administered daily for five consecutive days for an initial month and three consecutive days for subsequent months, wherein the purified sodium chlorite is at least 97% pure, 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, wherein the chlorite composition comprises disodium hydrogen phosphate and has a pH between 7.5 and 9.5, and wherein the subject (a) is between 40 and 65 years of age, (b) has a plasma hs-CRP level of at least 1.13 mg / L, (c) has been experiencing symptoms of ALS for at least 18 months prior to administration of the chlorite composition, and (d) has been experiencing symptoms of ALS for at least 18 months prior to administration of the chlorite composition. (e) absence of mutations in ALS-associated genes and SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CH Provided herein are methods in which the patient has at least one ALS response element selected from not having a mutation in CHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD.In a further aspect, a method of treating amyotrophic lateral sclerosis (ALS) in a subject may include intravenously administering to the subject a chlorite composition comprising purified sodium chlorite, wherein the chlorite composition is administered at 4 mg (or more) chlorite per kg body weight of the subject, wherein the chlorite composition is administered daily for five consecutive days for an initial month and three consecutive days for subsequent months, wherein the purified sodium chlorite is at least 97% pure, wherein the purified sodium chlorite comprises 2.0% or less sodium chloride, wherein the purified sodium chlorite comprises 1.0% or less sodium chlorate, wherein the chlorite composition comprises disodium hydrogen phosphate and has a pH between 7.5 and 9.5, and wherein the subject (a) is between 40 and 65 years of age, (b) has a plasma hs-CRP level of at least 1.13 mg / L, and (c) has symptoms of ALS for at least 18 months prior to administration of the chlorite composition. (d) not having inherited ALS pathology; (e) not having mutations in ALS-associated genes and not having any of the following: SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, N and having at least one ALS response factor selected from not having a mutation in EK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD.

[0010] Incorporation by Reference 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.

[0011] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description, which sets forth illustrative embodiments, and the accompanying drawings, in which the principles of the disclosure are utilized. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 shows a flow chart summarizing the distribution of subjects within the study.

[0013] [Diagram 2] FIG. 2 shows a graph of the change from baseline in ALSFRS-R score for subjects treated with a pharmaceutical composition comprising sodium chlorite (NP001) versus placebo.

[0014] [Diagram 3] FIG. 3 shows a graph of the change in lung capacity in subjects treated with a pharmaceutical composition comprising sodium chlorite (NP001) versus placebo.

[0015] [Figure 4] FIG. 4 shows a bar graph of progression-free rates for subjects treated with a pharmaceutical composition comprising sodium chlorite (NP001) versus placebo.

[0016] [Diagram 5] FIG. 5 shows the age distribution chart of subjects who remained progression-free during the study.

[0017] [Figure 6] FIG. 6 shows a flow chart summarizing the subject distribution of participant allocation combinations within the study.

[0018] [Figure 7]FIG. 7 shows a graph of the change from baseline in ALSFRS-R score for patients aged 40-65 years with plasma CRP of at least 1.13 mg / mL or greater treated with a pharmaceutical composition comprising sodium chlorite (NP001) versus placebo.

[0019] [Figure 8] FIG. 8 shows a graph of the percent change from baseline in vital capacity in patients aged 40-65 years with plasma CRP of at least 1.13 mg / mL or greater treated with a pharmaceutical composition comprising sodium chlorite (NP001) versus placebo.

[0020] [Figure 9] FIG. 9 shows a bar graph of progression-free rate versus placebo for subjects aged 40-65 years with plasma CRP of at least 1.13 mg / mL or greater treated with a pharmaceutical composition comprising sodium chlorite (NP001). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] Detailed Description This application describes ALS pathology and interactions with the pharmaceutical composition comprising sodium chlorite (NP001) that explain the plausible mechanism of action of treatment of ALS with the pharmaceutical composition comprising sodium chlorite (NP001), and describes ALS patient subpopulations that are likely to be responsive to treatment with the pharmaceutical composition comprising sodium chlorite (NP001). This application further describes identification of ALS symptoms and symptom onset, evaluation of ALS patients using the ALSFRS-R rating scale, quantification of plasma CRP levels in patients, quantification of lung capacity in patients, methods of treatment with the pharmaceutical composition comprising sodium chlorite (NP001), preparation of chlorite compounds, and chlorite pharmaceutical formulations. Finally, this application describes representative examples of the efficacy of treatment with the pharmaceutical composition comprising sodium chlorite (NP001) in various ALS patient subpopulations, and supporting data.

[0022] ALS pathology and its interaction with a pharmaceutical composition (NP001) containing sodium chlorite as an oxidant and immune system modulator Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with inappropriate immune system dysfunction, including NF-kB activation, proinflammatory factor production, and progressive changes in motor neuron function. As a common model, factors produced by spinal microglia have been identified that both damage and inhibit repair of neurons injured by the accumulation of misfolded proteins. The recent description that monocyte subsets in ALS patients become more activated over time, as reflected by HLA-DR cell surface levels, confirms our previous research that innate immune dysfunction is involved in disease progression. Therefore, drugs that interfere with or modulate this process may have therapeutic impact on the disease.

[0023] Although the cause of ALS remains largely unknown, data indicates the involvement of inflammation and immune system dysregulation 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 reverting macrophages to their inactivated state, may be effective in treating ALS.

[0024] Macrophages are white blood cells produced by the division of monocytes; monocytes and macrophages are phagocytes that play a role in innate immunity (non-specific immune defense) as well as in helping to initiate adaptive immunity (specific defense mechanisms). These cells phagocytose (engulf and then digest) cellular debris and pathogens as either stationary or mobile cells. When activated by pathogens or by other mechanisms, macrophages stimulate lymphocytes and other immune cells to recruit and respond. Activated macrophages are involved in the progression of several diseases and disorders, including amyotrophic lateral sclerosis (ALS). Activated macrophages induce massive leukocyte infiltration, flooding the surrounding tissue with inflammatory mediators, proapoptotic factors, and matrix-degrading proteases. These actions can result in inflammation, which can degrade tissue to a degree that causes serious damage. Tissue destruction caused by macrophage-driven inflammation, a form of immune system dysregulation, has been linked to the progression of the degenerative disease ALS.

[0025] Oxidizing agents, such as chlorite, can revert macrophages to their inactivated state, and chlorite can be used to treat a variety of diseases or conditions where immune system dysregulation is implicated in the disease pathology.

[0026] For example, chlorite can be used to treat amyotrophic lateral sclerosis (ALS), a macrophage-associated disease. However, the efficacy of chlorite treatment may vary within the ALS patient population. A pharmaceutical composition (NP001) containing sodium chlorite may include an intravenous (iv) formulation of purified, pH-adjusted sodium chlorite, which, without being bound to a particular theory, can be rapidly converted to taurine chloramine, a known regulator of nuclear factor kappa B (NFkB) activation. In vitro, chloramine levels in macrophages increase rapidly and remain elevated, and in vivo immunomodulatory activity has been documented to persist for several weeks. Unlike anti-inflammatory drugs such as hydrocortisone, chlorite does not cause global immunosuppression, but rather redirects activation toward wound healing, a phagocytic state, through upregulation of heme-oxygenase 1 (HO1).

[0027] Sodium chlorite is noteworthy as an oxidizing agent utilized in the treatment of diseases in which inflammation and immune system dysregulation are believed to be significant contributing factors in disease progression, including ALS. For example, activated macrophages are believed to be a form of immune system dysregulation involved in the progression of ALS, as they induce massive leukocyte infiltration and flood the surrounding tissue with inflammatory mediators, proapoptotic factors, and matrix degrading proteases. These actions can lead to inflammation, which can degrade tissue to a degree that causes severe damage. Tissue destruction carried out by macrophage-induced inflammation, a form of immune system dysregulation, has been linked to the progression of ALS, a neurodegenerative disease. In the presence of heme-bound iron, sodium chlorite is converted from a prodrug through a hypochlorite intermediate to the intracellular form of taurine chloramine (TauCl), likely due to NADPH oxidase complexes on the surface of phagocytic cells. TauCl is a long-lived effector molecule in macrophages that downregulates NF-kB expression and inhibits the production of pro-inflammatory cytokines, in part through activation of heme oxygenase-1 (HO-1).

[0028] ALS patients can be defined by four generalized patient groups: slow-progressing, fast-progressing, early disease-presenting, and late disease-presenting. Challenges associated with developing treatments for ALS include clinical trials that mix together various members of the ALS patient population from these categories, especially when employed from the earliest stages of disease onset. This has generally been the approach to patient selection for clinical trials, since it is believed that treatment outcomes are more likely to be favorable if introduced early in disease progression. However, there are characteristics of various ALS patient groups that may affect the ability to determine whether any drug has subset-specific activity important for modulating ALS disease in that ALS patient group, and those characteristics may not be present in another or all other ALS patient groups. Given that small study sizes are typical in ALS trials, the presence of individuals with confounding characteristics, even in small numbers, may lead to the failure of a drug that may have documented disease-modifying activity if properly targeted. Additionally, a further challenge with past clinical trials has been the reliance on only one positive clinical outcome category, e.g., ALSFRS-R score, to assess the general efficacy of a drug for ALS; as disclosed and embodied in some of the methods of patient selection herein, it may be beneficial to measure multiple clinical outcome categories to assess the efficacy of an ALS drug.

[0029] Of the four categories, only the subset called slow progression is seen to have an inflammatory component as a significant aspect of ALS disease pathology. The association of the slow progression subset with inflammation is inferred in ALS studies in association with CRP levels over time from diagnosis. The longer ALS patients survive after diagnosis, the higher their plasma CRP. There is a large subgroup of ALS patients with ongoing and possibly growing evidence of inflammation that progresses at a slower rate than seen in standard ALS clinical trials recruiting very early stage patients. In the context of drug development targeting ALS patients in whom inflammation may play a pathogenic role, the extent to which this patient population can be identified prior to clinical trial enrollment is a challenge. The data presented in this application defines an ALS patient population that is responsive to immunomodulatory approaches.

[0030] Disclosed herein are methods for the treatment of ALS patient populations that are responsive to immunomodulatory approaches, for example, treatment of slow-progressing ALS patient populations with pharmaceutical compositions that include sodium chlorite.

[0031] Disclosed herein are compositions and methods for treating subjects with ALS using chlorite. - Chlorites (compounds) are compounds that contain this group, where the oxidation state of chlorine is +3. Chlorites are also known as salts of chlorous acid. Chlorine is converted to the corresponding anion Cl - , ClO - , ClO2 - , ClO3 - , or ClO4 - It can have oxidation numbers of -1, +1, +3, +5, or +7, which are commonly known as chloride, hypochlorite, chlorite, chlorate, and perchlorate, respectively. As used herein, the term chlorite also includes pharma- ceutically acceptable salts of chlorite (e.g., NaClO2).

[0032] Sodium chlorite has previously been investigated for the treatment of patients with amyotrophic lateral sclerosis (ALS) in randomized Phase II clinical trials, including NP001, a pH-adjusted IV formulation of purified sodium chlorite. NP001 was found to be generally safe and well tolerated, but the trial was halted after results showed no significant slowing of disease progression across the patient population.

[0033] NP001 Drug Product (DP) is a clear, colorless, sterile solution of sodium chlorite and contains no preservatives. NP001 DP contains purified sodium chlorite (5.61 mg / mL, 62 mM), disodium hydrogen phosphate (0.107 mg / mL), and sterile water for injection, at pH 7.5-9.5. The active moiety is chlorite, and all clinical doses are expressed as mg / kg chlorite. A concentration of 5.61 mg / mL of sodium chlorite (62 mM) converts to 4.2 mg / mL of chlorite (62 mM). The formulation is packaged in 30 mL type 1 flint glass vials with 20 mM stoppers and capped with a red aluminum overseal. Each single-use 30 mL vial delivers 20 mL (nominal) of NP001. The formulation is not intended for IV administration undiluted. Dose preparation instructions specify that prior to administration, the formulation is combined with 0.45% sodium chloride (half normal saline obtained from a commercial supplier) to obtain an exact total volume of 250 mL of infusion solution.

[0034] In the data and examples provided herein, sodium chlorite, an immunomodulatory agent, in ALS patients shows dose-dependent modulation of blood cell-related activation markers.After intravenous administration of sodium chlorite formulation (NP001), 24 hours after a single dose, blood monocyte activation markers CD16 and HLA-DR are down-regulated in a dose-dependent manner.There is no drug-related hematological toxicity or drug-related SAE (adverse event).

[0035] The present disclosure provides a method for treating a subpopulation of patients suffering from amyotrophic lateral sclerosis (ALS) with chlorite, particularly sodium chlorite.Although a pharmaceutical composition comprising sodium chlorite may not be effective in all ALS patients, a pharmaceutical composition comprising sodium chlorite is effective in slowing disease progression at least across a subpopulation of ALS patients or more, and identifying a responsive subpopulation of ALS patients may lead to a safe and effective treatment of ALS.Therefore, the present disclosure provides a method for identifying a subpopulation of ALS patients and treating it using a salt of chlorite.

[0036] Without being bound by any theory, treatment with NP001 (sodium chlorite) can reduce both systemic inflammation and migration of blood monocytes to the spinal cord, key processes believed to be crucial in the progression of ALS, and has the potential to slow disease progression. As an oxidant, sodium chlorite may function by reverting activated macrophages to their inactivated state.

[0037] In targeted ALS patient subpopulations in which disease progression appears to be associated with inflammation and immune system dysregulation, as evidenced by clinically significant increases in CPR levels in the targeted ALS patient subpopulations, NP001 may be effective in slowing or halting disease progression by reducing inflammation and immune system dysregulation through the oxidation of activated macrophages back to their inactivated state.

[0038] Sporadic ALP and inherited ALS pathology There are multiple types of ALS that may be the cause of disease in a subject, which may be differentiated based on their signs, symptoms, genetic causes, lack of clear genetic association, or a combination of these. In some cases, subjects with ALS may be classified as sporadic or hereditary, where sporadic ALS pathology may occur in subjects with no genetic history (e.g., family history) of ALS, and hereditary ALS pathology may occur in subjects with a genetic history (e.g., family history) of ALS. Among ALS patients, subjects may be further characterized based on mutations to one or more genes. For example, mutations in the C9orf72 gene account for 30-40 percent of hereditary ALS in the United States and Europe, SOD1 gene mutations cause 15-20 percent of hereditary ALS worldwide, and TARDBP and FUS gene mutations each account for approximately 5 percent of hereditary ALS cases. Other genes associated with hereditary ALS also account for a small percentage of cases.

[0039] The majority of ALS cases are considered sporadic, occurring in subjects with no genetic history (e.g., family history) of ALS. As many as 90%-95% of ALS cases may be sporadic. Mutations in one or more genes may be associated with subjects experiencing either hereditary or sporadic ALS pathology. For example, 60 percent of individuals with familial ALS may have identified genetic mutations in one or more genes associated with the condition. In some cases, subjects experiencing either hereditary ALS pathology may have hereditary mutations in one or more of the following genes listed in the table below.

[0040] In some cases, C9orf72, SOD1, TARDBP, and FUS genes may be important for the normal function of motor neurons and other cells, and mutations in one or more of these genes may contribute to the decline in function or death of motor neurons in ALS patients.In some cases, one or more of the genes listed in Table X below may be important for the normal function of motor neurons and other cells, and mutations in one or more of these genes may contribute to the decline in function or death of motor neurons in ALS patients.Without being bound by a particular theory, mutations in one or more of these genes may contribute to the decline in function or death of motor neurons as a result of the accumulation of protein aggregates in motor neurons, the slowing of the transport of materials required for the proper function of axons in motor neurons, the accumulation of toxic substances in motor neurons, or a combination thereof. Table X [Table X-1] [Table X-2]

[0041] In some cases, the method of treatment disclosed herein is different based on the characterization of the subject's ALS pathology as sporadic or hereditary.In some cases, the method of treatment disclosed herein is different based on the characterization of the subject's ALS pathology as hereditary based on mutations in one or more genes associated with the condition.In some cases, the method of treatment disclosed herein is different based on the characterization of the subject's ALS pathology as sporadic or hereditary in combination with mutations in one or more genes associated with the condition.In some cases, the method of treatment disclosed herein is different based on the characterization of the subject's ALS pathology as hereditary, where the subject has hereditary mutations in one or more of the ALS-related genes, for example, one or more of the genes listed in Table X.

[0042] In some cases, subjects experiencing hereditary ALS pathology may progress more rapidly and begin to experience ALS symptoms earlier than subjects experiencing sporadic ALS pathology.In some cases, subjects experiencing ALS that experience hereditary ALS pathology may be less likely to respond to treatment with chlorite.In some cases, subjects experiencing ALS that experience sporadic ALS pathology may be more likely to respond to treatment with chlorite.In some cases, subjects experiencing ALS that experience sporadic ALS pathology may have a genetic mutation in one or more of ALS-related genes, such as the genes listed in Table X.In some cases, subjects experiencing ALS that experience sporadic ALS pathology may lack a genetic mutation in one or more of ALS-related genes, such as the genes listed in Table X.

[0043] In some cases, the methods of treatment disclosed herein include determining whether a subject has sporadic or hereditary ALS pathology, and treating the subject with chlorite if the subject has sporadic ALS pathology. In some cases, the methods of treatment disclosed herein include determining whether a subject has sporadic or hereditary ALS pathology, and not treating the subject with chlorite if the subject has hereditary ALS pathology. In some cases, the methods of treatment disclosed herein include determining whether a subject has a mutation in one or more ALS-associated genes, and treating the subject with chlorite if the subject has a mutation in one or more ALS-associated genes, where the one or more ALS-associated genes are SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP , UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, and ALS-FTD.In some cases, the methods of treatment disclosed herein include determining whether the subject has a mutation in one or more ALS-associated genes, and not treating the subject with chlorite if the subject has a mutation in one or more ALS-associated genes, where the one or more ALS-associated genes are SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP , UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, and ALS-FTD. In some cases, the methods of treatment disclosed herein include determining whether the subject has sporadic or inherited ALS pathology and whether the subject has a mutation in one or more ALS-associated genes, where the one or more ALS-associated genes are SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIG The ALS-related genes include MAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, and ALS-FTD. In some cases, the genetic mutation is inherited in an autosomal dominant pattern. In some cases, the mutation in one or more ALS-related genes is an inherited mutation. In some cases, the genetic mutation is inherited in an autosomal recessive pattern.In some cases, the genetic mutation is inherited in an X-linked dominant pattern.

[0044] Parameters of ALS patient subpopulations Disclosed herein are several methods for identifying ALS patient subpopulations that are likely to be responsive to treatment with pharmaceutical compositions comprising sodium chlorite.The characteristics of responsive patient subpopulations are diverse and can include patient age, patient C-reactive protein (CRP) level, duration from onset of ALS symptoms, and combinations thereof.In some cases, responsive patient subpopulations can be further defined by elevated levels of other inflammatory biomarkers.

[0045] In an exemplary embodiment, the ALS patient subpopulation that is responsive to treatment with a pharmaceutical composition comprising sodium chlorite includes patients ages 40-65 years and stable disease patients with elevated C-reactive protein (CRP) levels of at least 1.13 mg / L or greater. In some cases, the ALS patient subpopulation has a post-onset ALS symptom duration of at least 12 months. In some cases, the ALS patient subpopulation has a post-onset ALS symptom duration of at least 18, 21, or 24 months.

[0046] In an exemplary embodiment, the ALS patient subpopulation that is responsive to treatment with a pharmaceutical composition comprising sodium chlorite includes patients with stable disease who have elevated C-reactive protein (CRP) levels above 3 mg / L. In some cases, the ALS patient subpopulation is 40-65 years old. In some cases, the ALS patient subpopulation also has a post-onset ALS symptom duration of at least 12 months. In some cases, the ALS patient subpopulation has a post-onset ALS symptom duration of at least 18, 21, or 24 months.

[0047] In an exemplary embodiment, the ALS patient subpopulation responsive to treatment with a pharmaceutical composition comprising sodium chlorite includes patients aged 45-60 years. In some cases, the ALS patient subpopulation has elevated C-reactive protein (CRP) levels of greater than 1.13 mg / L. In some cases, the ALS patient subpopulation has elevated C-reactive protein (CRP) levels of greater than 3 mg / L. In some cases, the ALS patient subpopulation has a post-onset duration of ALS symptoms of at least 12 months. In some cases, the ALS patient subpopulation has a post-onset duration of ALS symptoms of at least 18, 21, or 24 months.

[0048] In an exemplary embodiment, the ALS patient subpopulation that is responsive to treatment with a pharmaceutical composition comprising sodium chlorite includes patients with an ALS symptom onset duration of at least 12 months. In some cases, the ALS patient subpopulation has an ALS symptom onset duration of at least 18, 21, or 24 months. In some cases, the ALS patient subpopulation has an elevated C-reactive protein (CRP) level of greater than 1.13 mg / L. In some cases, the ALS patient subpopulation has an elevated C-reactive protein (CRP) level of greater than 1.13 mg / L. In some cases, the ALS patient subpopulation is 40-65 years old.

[0049] In some cases, ALS patient subpopulations that are responsive to treatment with pharmaceutical compositions that include sodium chlorite may also include patients with elevated levels of other inflammatory biomarkers. These inflammatory markers may include, but are not limited to, tumor necrosis factor (e.g., TNF-alpha), monocyte chemotactic protein (e.g., MCP-1), interleukins (e.g., IL-6, IL-12), and chemokine ligands (e.g., CXCL1). These inflammatory proteins may be produced by an array of lymphocytes, including T cells, monocytes, and macrophages. In some cases, ALS patient subpopulations that are responsive to treatment with pharmaceutical compositions that include sodium chlorite may have elevated levels of: circulating (e.g., plasma) proinflammatory, antiinflammatory, and regulatory cytokines, IL-4, IL-6, IL-10, soluble IL-2 receptor, soluble IL-6 receptor, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-1, and / or IL-1 receptor antagonist. In some cases, the ALS patient subpopulation that responds to treatment with the pharmaceutical composition comprising sodium chlorite has elevated inflammatory biomarker IL-18 and is positive for LPS at baseline.In some cases, the ALS patient subpopulation that responds to treatment with the pharmaceutical composition comprising sodium chlorite has elevated levels of one or more of the inflammatory biomarkers listed above, which are twice as high as baseline when compared with the ALS patient population that does not respond to treatment with the pharmaceutical composition comprising sodium chlorite.In some cases, these plasma markers include IL18, gamma interferon, IL6, and CRP.

[0050] It is plausible that in some cases, the disease mechanism and trajectory in younger patients (<40 years) at onset is different from that of older patients and is more likely to have a genetic or hereditary component, as is often the case in other chronic conditions, such as cancer and cardiovascular disease. With regard to the exclusion of older groups, it is believed that CRP levels increase with age and that the CRP sensitivity cutoff applied in the Phase 2 study of the pharmaceutical composition comprising sodium chlorite may have allowed for the over-representation of older ALS patients whose CRP values ​​measured other disease activities unrelated to ALS, thereby obscuring the ALS-specific activity of the pharmaceutical composition comprising sodium chlorite.

[0051] Measuring ALS Symptoms, Disease Progression, and Treatment Efficacy Disclosed herein are methods for identifying ALS symptoms and ALS symptom onset, monitoring and assessing ALS disease progression, and evaluating treatment efficacy based on ALS symptoms and ALS disease progression.

[0052] I. Identifying ALS Symptoms and Onset Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that destroys motor neurons in the brain and spinal cord, eventually causing muscle paralysis and death, usually within 2-4 years of diagnosis. ALS symptoms generally result from the gradual destruction of motor neurons and may include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, poor fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, poor coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, death of muscle cells, or a combination of two or more of these. Eventually, ALS patients lose the ability to move their limbs, walk, lift their head, and even breathe. Thus, ALS patients eventually become wheelchair bound and require assistance to perform all basic daily functions, such as dressing, walking, eating, and using the toilet, and ultimately require a tracheotomy and mechanical ventilator.

[0053] ALS symptoms are difficult to diagnose early because they are highly variable and may appear almost identical to fatigue symptoms in its early stages. It is also difficult to diagnose because the symptoms are often similar to those of other neurological diseases. For this reason, diagnosis is often achieved by ruling out other neurological diseases as the symptoms progress. Diagnosis generally begins with identification of the problem as a neurological problem and a neurological examination, followed by diagnostic tests to rule out other neurological conditions and confirm the presence of ALS. Such diagnostic tests may include EMG (electromyography) to test nerve conduction, MRI (magnetic resonance imaging) to image the spinal cord and surrounding nerves, muscle biopsy, and blood and urine tests to look for evidence of other diseases whose symptoms resemble early signs of ALS, such as thyroid and parathyroid disease, vitamin B12 deficiency, HIV, hepatitis, autoimmune diseases, and other types of cancer. Creatine kinase (CK), a muscle enzyme released when muscles are damaged or die, is also measured because increased levels of CK indicate muscle death, a symptom of ALS. In some cases, a spinal fluid tap may also be used to test for abnormal cells in the spinal fluid.

[0054] For the purpose of determining whether a patient who has, for example, more than 12, 18, or 24 months of symptom onset after ALS diagnosis is part of the target ALS patient population, their identification can include reviewing the subject's medical history for ALS symptoms, reviewing the subject's medical history for ALS diagnosis, or asking the subject about when they first began to experience ALS symptoms. Directly asking the subject about when they think they first began to experience symptoms can be useful because it can identify ALS symptoms that many patients recall having experienced, but may not be reflected in their medical history, at a date before the first reported symptoms in their medical history or before the date of their formal ALS diagnosis.For example, a patient may report that, at the date of qualifying the patient as part of the target ALS patient population, they have experienced one or more of the above-identified ALS symptoms, for example, for at least 12 months or longer after the onset of symptoms, at least 18 months or longer after the onset of symptoms, or at least 21 months or longer after the onset of symptoms.

[0055] II. Patient evaluation using ALSFRS-R scores ALS disease progression is commonly monitored by using the ALSFRS-R (ALS Functional Rating Scale-Revised) score. The ALSFRS-R is a questionnaire-based scale that measures and tracks changes in a patient's physical function over time. The ALSFRS-R score is widely used to monitor disease progression in clinical trials and patient treatments.

[0056] The ALSFRS-R score measures 12 aspects of physical function including speech, salivation, swallowing, writing, cutting food, climbing stairs, turning in bed, walking, dressing and hygiene, respiratory distress (difficulty breathing), orthopnea (shortness of breath while lying down), and respiratory failure. Each function is scored from 4 (normal) to 0 (no ability), and then each value is summed to obtain a score with a maximum score of 48 and a minimum score of 0. The higher the score, the better the patient's physical functionality and the less ALS has progressed within the patient.

[0057] ALSFRS-R score can be measured in patients by questionnaire or physical examination and observation of work performed by medical personnel.For example, with respect to speech, score 4 can represent normal speech, score 3 can represent audible impairment in speech, score 2 can represent speech that can be understood by repetition, score 1 can represent speech with non-verbal communication, and score 0 can represent loss of practical speech.In swallowing evaluation, score 4 can represent normal swallowing, score 3 can represent occasional choking, score 2 can represent dietary modification, score 1 can indicate the need for a feeding tube, and score 0 can represent exclusively parenteral or enteral nutrition.Methods for determining ALSFRS-R score are well known in the art, and any suitable method for assessing ALSFRS-R score can be utilized to evaluate a subject.

[0058] Assessment of the patient's ALSFRS-R score can be used to assess disease progression after treatment with a pharmaceutical composition comprising sodium chlorite and to classify the patient as a responder or non-responder based on disease progression. A reduction of 0 to 1 point in the ALSFRS-R score after treatment with a pharmaceutical composition comprising sodium chlorite over a period of approximately 6 months can indicate that ALS disease progression has been slowed or stopped, thereby qualifying the patient as a responder.

[0059] III. Quantification of Patient CRP Levels Elevated CRP levels are commonly used as a marker of underlying inflammation. [Table 1-1] [Table 1-2]

[0060] Patient CRP level is a metric that is utilized in evaluating ALS patients as members of the target ALS patient population. Because neurodegenerative disease is believed to progress in the target patient population based in part on inflammation and immune system dysregulation, patient CPR level is used to identify patients who experience inflammation and immune system dysregulation and are likely to be responsive to treatment with pharmaceutical compositions comprising sodium chlorite. Patient CPR level is determined by analysis of CPR plasma content, and a CPR level above 3 mg / L represents a clinically significant elevated CRP level. Patients with CRP levels above 3 mg / L may be members of the target ALS patient population who are likely to be responsive to treatment with pharmaceutical compositions comprising sodium chlorite.

[0061] Various methods of screening patient CRP plasma content can be utilized in this embodiment to determine whether a patient is a member of the target ALS patient population. Patient CRP plasma content is generally determined using blood tests. Non-limiting methods of screening patient CRP levels can include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reaction, or high-sensitivity near-infrared particle immunoassay rate method. However, any other suitable method for quantitatively determining that patient CRP level is at least 3 mg / L or more can be utilized in this embodiment to determine whether a patient is a member of the target ALS patient population.

[0062] IV. Quantification of vital capacity Vital capacity is the maximum volume of air that can be exhaled from the lungs after a maximal inhalation. As ALS progresses, the motor neurons that control the diaphragm succumb to the disease, and the patient loses the ability to breathe unassisted, eventually undergoing tracheotomy and mechanical ventilation to prolong the patient's life. Reductions in vital capacity, including percent change from baseline in vital capacity, can be used to measure ALS disease progression. Vital capacity is approximately 4800 mL and varies with age and body size. It can be calculated by summing tidal volume, inspiratory reserve volume, and expiratory reserve volume. VC=TV+IRV+ERV. A given patient's vital capacity can be measured using a spirometer, or other device known in the art, and measuring vital capacity can be useful to assess a given patient's ALS disease progression. Other non-limiting methods of measuring lung capacity include spirometry, or forced expiratory volume testing, but any other suitable method for quantitatively determining changes in a patient's lung capacity can be utilized to assess ALS disease progression and treatment effectiveness according to the embodiments disclosed herein.

[0063] In ALS patients, the decline in respiratory vital capacity translates directly into survival outcomes. Similar to the variability seen in ALSFRS-R score comparisons, changes in respiratory function in ALS patients are reproducible over time, regardless of whether the measure is FVC or SVC. Natural history studies of VC in ALS patients over time identify an average 2.5-3% decline in function per month.

[0064] Preparation of Chlorite Compounds for Patient Treatment For example, the exemplary method of preparing and purifying chlorite for use in pharmaceutical preparations is described herein, including the pharmaceutical composition comprising sodium chlorite.The method of preparing chlorite, the method of preparing the chlorite compound with the required purity and pH for use in pharmaceutical preparations, and the pharmaceutical preparation comprising chlorite, for example the pharmaceutical composition comprising sodium chlorite, are disclosed.

[0065] I. Method of Preparation The method of purifying chlorite is described herein.It is intended that the method described herein can be used to produce the formulation or pharmaceutical preparation described herein.However, the formulation and pharmaceutical preparation described herein can also be produced by other methods, and the formulation and pharmaceutical preparation described herein is not limited to those produced by the method described herein.

[0066] In some variations, the purification is by subjecting the mixture containing chlorite to conditions in which chlorite is in solution but one or more impurities are insoluble. The chlorite is separated from the insoluble impurities. In some variations, the chlorite is further purified by crystallization from the mixture of chlorite and separation of the chlorite from the remaining mixture. In some variations, the chlorite is purified from the mixture containing sodium chlorite.

[0067] Generally, chlorite ion can be derived from any source that contains chlorite.For example, chlorite can be a salt of chlorite, such as an alkali metal salt, sodium chlorite, potassium chlorite, etc., or a mixture of salts of chlorite.Alternatively, the source of chlorite can be derived from a preparation that contains chlorite.In some variations, chlorite is purified from a preparation that contains a pharmaceutical composition that contains sodium chlorite, TCDO or WF10.In another variation, chlorite is derived from a solution that contains sodium chlorite.

[0068] In some variations, impure chlorite, including but not limited to impure sodium chlorite, is dissolved in a solvent or solvent system. In some variations, any solvent is used in which chlorite dissolves. In other variations, any solvent is used in which chlorite dissolves and in which chlorite does not react. In some variations, the solvent is distilled water. In some variations, the solvent is a non-organic solvent.

[0069] In some variations, the impure sodium chlorite is from about 0.1% to about 99% by weight of the starting material. As non-limiting examples of the purity of the chlorite starting material, the chlorite is about 0.1% to about 5%, about 1% to about 5%, about 4% to about 10%, about 1% to about 15%, about 15% to about 25%, about 5% to about 25%, about 25% to about 50%, about 50% to about 75%, about 75% to about 85%, about 85% to about 95%, about 60% to about 90%, about 95% to about 99% by weight of the starting material, and is at least about 50% or more, at least about 60% or more, at least about 70% or more, at least about 80% or more, at least about 90% or more, or at least about 95% or more pure. When impure chlorite is present in a solvent, the purity percentage is relative to the non-solvent components. In some variations, the chlorite is about 75% to about 85% pure. In some variations, the chlorite is about 85% to about 95% pure. In some variations, the chlorite is at least about 85% or more pure.

[0070] In some variations, a small amount of hydrogen peroxide is added to the dissolved chlorite.Without wishing to be bound by theory, the addition of a small amount of hydrogen peroxide can reduce sodium chlorite to sodium chlorite.If desired, unreacted hydrogen peroxide can then be removed.In some variations, hydrogen peroxide is added after the initial chlorite dissolution step, and then removed by filtration, for example, centrifugal filtration.

[0071] Briefly, one method of preparing a formulation comprising chlorite as disclosed herein can be achieved through the steps of (a) concentrating a chlorite solution at a temperature of 60°C to about 100°C, thereby precipitating impurities from the solution, (b) removing impurities from the concentrated solution by filtration, (c) inducing crystallization of chlorite from the concentrated solution, (d) recovering the resulting chlorite solid by filtration, and (e) dissolving the chlorite solid in an aqueous solvent. In some variations, it is envisioned that the resulting aqueous formulation of chlorite comprises a purity of at least 80% or more chlorite, at least 85% or more chlorite, at least 90% or more chlorite, at least 95% or more chlorite, or at least 99% or more chlorite. However, embodiments of the present disclosure are not limited thereto, and any suitable method of preparing chlorite or its pharma- ceutically acceptable salt can be utilized.

[0072] II. Chlorite Purity and pH The present disclosure describes compositions and methods using chlorite formulated in an aqueous solution where chlorite is more than 95% pure.In some cases, chlorite can be more than 97%, more than 99%, more than 99.5%, or more than 99.9% pure.In some cases, chlorite can be at least 95% or more, at least 97% or more, at least 99% or more, at least 99.5% or more, or at least 99.9% or more pure.As used herein, the "purity" of chlorite in a sample is calculated as the weight percentage of chlorite salt relative to the total weight of the sample.When determining the purity of chlorite in a solution, the weight of the solvent (e.g., water in an aqueous solution) is not included.Purity can be evaluated by calibrated integrals of each peak in a compound or formulation, such as chlorite, chloride, chlorate, phosphate, and sulfate, using ion chromatography and ion detection equipment. For example, chlorite is commercially available as Sodium Chlorite, Technical Grade, 80% purity (catalog number 244155, Sigma-Aldrich).

[0073] Alternatively, crystalline sodium chlorite is provided with a purity of greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, greater than 99.5%, or greater than 99.9%. Solid pharmaceutical formulations that include crystalline sodium chlorite in a purity of greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, greater than 99.5%, or greater than 99.9% in addition to one or more pharmaceutical excipients are also encompassed.

[0074] Chlorite formulations for use in the present disclosure may contain small amounts of chlorite, sulfate, or chloride. As used herein, a formulation is "substantially free" of a molecule when the molecule constitutes less than one part per thousand by weight of non-solvent molecules in the formulation. In certain embodiments, the weight ratio of chlorite to chlorate is greater than 100:1.5, greater than 100:0.5, greater than 100:1, or greater than 100:0.1. In one embodiment, the composition is substantially free of chlorite. In another embodiment, the weight ratio of chlorite to chloride is greater than 100:45.5, or greater than 100:8.5. In one embodiment, the composition is substantially free of chloride. In a further embodiment, the weight ratio of chlorite to sulfate is greater than 100:16.4, or greater than 100:1.6. In one embodiment, the composition is substantially free of sulfate.

[0075] The pH of the chlorite formulation for use in the present disclosure may be adjusted to about 7 to about 11.5. In some embodiments, the pH of the chlorite formulation is lowered to about 7 to 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.

[0076] Also described herein are methods for preparing chlorite formulations and pharmaceutical formulations, including but not limited to the chlorite formulations specifically described herein.Also described herein are kits and methods for administering the formulations and pharmaceutical formulations described herein.Various exemplary aspects and variations of the present disclosure are described elsewhere herein, including but not limited to the "Summary" and examples.It is also understood that the present disclosure includes embodiments that include, consist essentially of, and / or consist of one or more elements described herein.

[0077] In some embodiments, the present disclosure utilizes an aqueous formulation comprising chlorite. In some embodiments, the chlorite formulation comprises an aqueous solvent and, optionally, one or more other solvents for chlorite. In some embodiments, the formulation comprises chlorite and an aqueous solvent for chlorite, and has a pH of about 7 to about 11.5.

[0078] The solvent or combination of solvents for use in the formulations described herein can be determined by various methods known in the art.One non-limiting example includes: (1) theoretically estimating the solubility parameter value of the solvent and selecting one that matches chlorite using standard equations in the art; (2) experimentally determining the saturated solubility of chlorite in the solvent; (3) selecting one or more that exhibit desired solubility; and (4) selecting the solvent or solvents that do not reduce the activity of chlorite or do not react or only minimally react with chlorite.In some embodiments, the liquid formulations described herein comprise multiple solvents.

[0079] In some embodiments, the chlorite formulation comprises an aqueous solvent. In some variations, water is the primary solvent in the aqueous formulation. In some variations, water is at least about 50% or more by volume of the solvent component of the aqueous formulation. In some variations, water is at least about 50% or more by volume of the aqueous formulation. In some variations, water is at least about 50% or more by volume of the solvent component. In some variations, water is at least about 50 to about 60 volume percent, about 60 to about 70 volume percent, about 70 to about 80 volume percent, about 80 to about 90 volume percent, about 90 to about 99 volume percent, at least about 50 volume percent or more, at least about 60 volume percent or more, at least about 70 volume percent or more, at least about 80 volume percent or more, at least about 90 volume percent or more, or at least about 95 volume percent or more, about 50 volume percent, about 60 volume percent, about 70 volume percent, about 80 volume percent, about 90 volume percent, or about 95 volume percent of the solvent component. In some variations, the water is about 50 to about 60 volume percent, about 60 to about 70 volume percent, about 70 to about 80 volume percent, about 80 to about 90 volume percent, about 90 to about 99 volume percent, at least about 50 volume percent or more, at least about 60 volume percent or more, at least about 70 volume percent or more, at least about 80 volume percent or more, at least about 90 volume percent or more, or at least about 95 volume percent or more of the aqueous formulation. In some variations, the water is at least about 95 volume percent or more of the aqueous formulation. In some variations, the water is about 80 to about 90 volume percent of the aqueous formulation. In some variations, the water is about 90 to about 99 volume percent of the aqueous formulation.

[0080] Formulations may have different concentrations of chlorite.In some embodiments, the concentration of chlorite in formulation is high, and therefore it is diluted to a less concentrated form before administration.In some embodiments, the formulations described herein are approximately diluted at least about 2.5 times or more, about 5 times or more, about 7.5 times or more, about 10 times or more, about 20 times or more, about 25 times or more, about 50 times or more, about 100 times or more, about 200 times or more, about 250 times or more, about 300 times or more, about 500 times or more, or about 1000 times or more. In some embodiments, the formulations described herein are diluted about 2-fold to about 10-fold, about 10-fold to about 50-fold, about 50-fold to about 100-fold, about 100-fold to about 500-fold, or about 500-fold to about 1000-fold. In some embodiments, the formulations described herein are diluted about 2-fold to about 10-fold. In some embodiments, the formulations described herein are diluted about 10-fold to about 50-fold. In some embodiments, the formulations described herein are diluted about 7.5-fold. In some embodiments, the formulations described herein are diluted about 25-fold. In some embodiments, the formulations described herein are diluted about 200-fold.

[0081] In some embodiments, the concentration of chlorite in the formulations described herein is from about 1 μM to about 1.5 M. In other embodiments, the concentration of chlorite in the formulations described herein is from about 1 M to about 1.5 M, from about 1 μM to about 100 mM, from about 10 μM to about 100 mM, from about 0.1 mM to about 10 mM, from about 0.1 mM to about 500 mM, from about 0.1 mM to about 200 mM, from about 1 mM to about 100 mM, from about 0.1 mM to about 5 mM, from about 50 mM to about 100 mM, from about 55 mM to about 70 mM, or from about 60mM to about 65mM, about 100mM to about 500mM, about 200mM to about 400mM, about 300mM to about 700mM, about 1mM, about 1.5mM, about 2mM, about 2.5mM, about 3m M, about 3.5mM, about 4mM, about 5mM, about 10mM, about 20mM, about 30mM, about 40mM, about 50mM, about 60mM, about 62mM, about 65mM, about 70mM, about 80mM, about 90mM, about 100mM, at least about 0.1mM or more, at least about 1mM or more, at least about 2mM or more, at least about 5mM or more, at least about 10mM or more, at least about 20mM or more, at least about 30mM or more, at least about 40mM or more, at least about 50mM or more, at least about 60mM or more, at least about 70mM or more, at least about 80mM or more, at least about 90mM or more, or at least about 100mM or more.In a preferred embodiment, the concentration of chlorite in the formulation described herein is about or at least about 60mM or more.

[0082] In some embodiments, the concentration of chlorate in the formulations described herein is about 50 mM to about 100 mM. In some embodiments, the concentration of chlorate in the formulations described herein is about 55 mM to about 75 mM. In some embodiments, the concentration of chlorate in the formulations described herein is about 0.1 mM to about 10 mM. In some embodiments, the concentration of chlorate in the formulations described herein is about 1 mM to about 5 mM.

[0083] In some embodiments, the chlorite formulation has a pH of about 12.0 or less. In some embodiments, the pH of the formulation is about 11.5 or less, about 11.0 or less, about 10.5 or less, about 10.0 or less, about 9.5 or less, about 9.0 or less, about 8.5 or less, about 8.0 or less, about 7.5 or less, about 7.0 or less, about 6.5 or less, or about 6.0 or less. In some embodiments, the pH of the formulation is about 11.5 or less. In some embodiments, the pH of the formulation is about 10.5 or less. In some embodiments, the pH of the formulation is about 8.5 or less. In some embodiments, the pH of the formulation is about 7.5 or less. In some embodiments, the pH of the formulation is from about 7 to about 12, from about 7 to about 11.5, from about 7 to about 10.5, from about 7 to about 10, from about 7 to about 9.5, from about 7 to about 9.0, from about 7 to about 8.5, from about 7 to about 8.0, from about 7 to about 7.5, from about 7.5 to about 8, from about 7.5 to about 8.5, from about 7 to about 8, from about 8 to about 9, from about 7.0 to about 8.5, from about 8 to about 8.5, from about 8.5 to about 9, or from about 7. The pH of the chlorite formulation may be any one or more of: 1 to about 7.7, about 7.2 to about 7.6, about 7.3 to about 7.4, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8.0, about 8.1, about 8.2, about 8.3, about 8.4, about 8.5, about 8.6, about 8.7, about 8.8, or about 8.9. In some embodiments, the chlorite formulation has a pH of about 7.0 to about 9.0. In some embodiments, the chlorite formulation has a pH of about 7.0 to about 8.5. In some embodiments, the chlorite formulation has a pH of about 6.0 to about 8.5. In some embodiments, the chlorite formulation has a pH of about 7.0 to about 8.0. In some embodiments, the chlorite formulation has a pH of about 7.4. The chlorite formulation may have a pH that is at physiological levels.

[0084] In some embodiments, the chlorite formulation has a pH as described above and is formulated for any one or more of parenteral, systemic, or intravenous administration.In some embodiments, the chlorite formulation has a pH as described above and has a chlorite purity percentage as described herein.

[0085] In some embodiments, the formulations described herein have a pH as described above and a chlorite concentration as described herein. In some embodiments, the aqueous formulations described herein have a pH of about 7 to about 11.5, or about 7.0 to about 10, or about 7.0 to about 9.0, or about 7.0 to about 8.5, or about 7.1 to about 7.7, and a chlorite concentration of about 1 to about 100 mM. In some embodiments, the aqueous formulations described herein have a pH of about 7 to about 11.5, or about 7.0 to about 10, or about 7.0 to about 9.0, or about 7.0 to about 8.5, or about 7.1 to about 7.7, and a chlorite concentration of about 1 to about 5 mM. In some embodiments, the aqueous formulations described herein have a pH of about 7 to about 11.5, or about 7.0 to about 10, or about 7.0 to about 9.0, or about 7.0 to about 8.5, or about 7.1 to about 7.7, and a concentration of chlorite of about 50 to about 80 mM.

[0086] In some embodiments, the aqueous formulations described herein have a pH of about 7 to about 11.5, or about 7.0 to about 10, or about 7.0 to about 9.0, or about 7.0 to about 8.5, or about 7.1 to about 7.7, and the pH is adjusted with a pH adjuster that is one or more of phosphate or acetate.

[0087] In some embodiments, the formulations described herein are stable for at least about 1 day or more, at least about 2 days or more, at least about 3 days or more, at least about 4 days or more, at least about 5 days or more, at least about 6 days or more, at least about 1 week or more, at least about 2 weeks or more, at least about 3 weeks or more, at least about 4 weeks or more, at least about 5 weeks or more, at least about 6 weeks or more, at least about 7 weeks or more, at least about 8 weeks or more, at least about 1 month or more, at least about 2 months or more, at least about 3 months or more, at least about 4 months or more, at least about 5 months or more, or at least about 6 months or more in terms of one or more of pH or chlorite decomposition.In some embodiments, the formulations described herein are stable for at least about 1 week or more in terms of one or more of pH or chlorite decomposition. In some embodiments, the formulation described herein is stable for at least about one month or longer in terms of one or more of pH or chlorite decomposition.In some embodiments, the formulation described herein is stable in terms of one or more of pH or chlorite decomposition at one or more of room temperature, refrigerated conditions, or at approximately 4°C.In some embodiments, the formulation described herein is stable in terms of one or more of pH or chlorite decomposition under reduced light conditions or storage in a container that limits the amount of light to which the formulation is exposed.In some embodiments, the formulation described herein is stable in terms of one or more of pH or chlorite decomposition when stored in the dark.As used herein, examples of stable pH refer to the pH of the formulation changes by less than about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1 compared to the pH of the formulation as originally prepared. In some embodiments, the pH of the formulation changes by less than about 0.2 compared to the pH of the formulation as originally prepared. The pH can be measured, for example, using a pH meter. Examples of stable chlorite formulations include those in which, compared to the amount of chlorite present in the formulation as initially prepared, less than about 0.1%, less than about 0.2%, less than about 0.3%, less than about 0.4%, less than about 0.5%, less than about 0.6%, less than about 0.7%, less than about 0.8%, less than about 0.9%, less than about 1%, less than about 2%, less than about 3%, less than about 4%, less than about 5%, less than about 6%, less than about 7%, less than about 8%, less than about 9%, or less than about 10% of chlorite is decomposed into non-chlorite ions.In some embodiments, compared to the amount of chlorite present in the formulation as initially prepared, less than about 2% of chlorite is decomposed into non-chlorite compounds.In some embodiments, compared to the amount of chlorite present in the formulation as initially prepared, less than about 0.5% of chlorite is decomposed into non-chlorite compounds. The presence of non-chlorite components can be measured, for example, using gas chromatography (GC), mass spectrometry, or other methods known to those of skill in the art.

[0088] In some embodiments, the chlorite formulations described herein contain no more than about 5% by weight of harmful non-chlorite elements of other commercially available formulations. In some embodiments, the chlorite formulations described herein contain no more than about 4% by weight, no more than about 3% by weight, no more than about 2% by weight, no more than about 1% by weight, no more than about 0.5% by weight, no more than about 0.3% by weight, no more than about 0.25% by weight, no more than about 0.2% by weight, no more than about 0.1% by weight, no more than about 0.05% by weight, or no more than about 0.02% by weight of harmful non-chlorite elements of other commercially available formulations. In some embodiments, the chlorite formulations described herein contain no more than about 4% by weight of harmful non-chlorite elements of other commercially available formulations. In some embodiments, the chlorite formulations described herein contain no more than about 2% by weight of harmful non-chlorite elements of other commercially available formulations. In some embodiments, the chlorite formulations described herein contain no more than about 0.5% by weight of the harmful non-chlorite elements of other commercially available formulations.In some embodiments, the chlorite formulations described herein contain no more than about 0.05% by weight of the harmful non-chlorite elements of other commercially available formulations.In some embodiments, the chlorite formulations described herein are substantially free of the harmful non-chlorite elements of other commercially available formulations. Non-limiting examples of methods for detection of non-chlorite constituents include HPLC; SPCS, e.g., using a Novosep A2 column with 3.6 mM sodium carbonate as the mobile phase, 5μ, 250×4.0 mm, flow rate 0.8 mL / min; DS-Plus Suppressor, e.g., using a Novosep A2 column with 3.6 mM sodium carbonate as the mobile phase, 5μ, 250×4.0 mm, flow rate 0.8 mL / min; Allsep A-2 anion column, using 2.1 mM NaHCO3 / 1.6 mM Na2CO3 as the mobile phase, 100×4.6 mm, flow rate 2.0 mL / min; anion HC column, using 2.8 mM NaHCO3:2.2 mM Na2CO3 in 10% methanol as the mobile phase, 150×4.6 mm, flow rate 1.4 mL / min; or Allsep A-2 anion column, 5μ, 100×4.6 mm, using 2.1 mM NaHCO3 / 1.6 mM Na2CO3 as the mobile phase, with a flow rate of 1.0 mL / min.See, for example, the Grace Davison line of products and product information from Alltech Associates, Inc. for more information.

[0089] In some embodiments, the chlorite formulations described herein contain less than about 1.9% chloride ion. In some embodiments, the chlorite formulations contain less than about 1.9% by weight, less than about 1.8% by weight, less than about 1.5% by weight, less than about 1.0% by weight, less than about 0.5% by weight, less than about 0.3% by weight, less than about 0.1% by weight, less than about 0.05% by weight, less than about 0.01% by weight, less than about 0.001% by weight, about 0.001 to about 0.1% by weight, about 0.1 to about 0.5% by weight, about 0.5 to about 1.0% by weight, about 1.0 to about 1.5% by weight, or about 1.5 to about 1.8% by weight of chloride ion. In some embodiments, the chlorite formulations contain less than about 0.5% by weight of chloride ion. In some embodiments, the chlorite formulations contain less than about 0.24% by weight of chloride ion. In some embodiments, the chlorite formulation contains less than about 0.2% by weight of chloride ion. In some embodiments, the chlorite formulation contains less than about 0.1% by weight of chloride ion. In some embodiments, the chlorite formulation is substantially free of chloride ion. In some embodiments, the level of chloride ion is below the level of detection using HPLC.

[0090] In some embodiments, the chlorite formulation contains less than about 1.5% chlorate ion. In some embodiments, the chlorite formulation contains 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%, about 0.001 to about 0.1%, about 0.001 to about 0.01%, about 0.01 to about 0.1%, about 0.1 to about 0.5%, about 0.5 to about 1.0%, or about 1.0 to about 1.4% chlorate ion. In some embodiments, the chlorite formulation is substantially free of chlorate ion. In some embodiments, the chlorite formulation contains less than about 0.5% chlorate ion by weight. In some variations, the chlorite formulation is substantially free of chlorate ion. In some embodiments, the chlorite formulation contains less than about 0.19% chlorate ion by weight. In some embodiments, the chlorite formulation contains less than about 0.1% by weight of chlorate ion. In some embodiments, the level of chlorate ion is below the level of detection using HPLC.

[0091] In some embodiments, the chlorite formulation contains less than about 0.7% sulfate ion. In some embodiments, the chlorite formulation contains 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%, about 0.001 to about 0.1%, about 0.01 to about 0.1%, about 0.01 to about 0.5%, about 0.06 to about 0.08%, or about 0.5 to about 0.65% sulfate ion. In some embodiments, the chlorite formulation contains about 0.5 to about 0.65% sulfate ion. In some embodiments, the chlorite formulation is substantially free of sulfate ion. In some embodiments, the chlorite formulation contains less than about 0.5% by weight of sulfate ion. In some embodiments, the chlorite formulation is substantially free of sulfate ion. In some embodiments, the chlorite formulation contains less than about 0.08% by weight of sulfate ion. In some embodiments, the level of sulfate ion is below the level of detection using HPLC.

[0092] In some embodiments, the chlorite formulations described herein include phosphate ions. In some embodiments, the chlorite formulations described herein include sodium ions. In some embodiments, the chlorite formulations include chlorite, an aqueous solvent, sodium, and phosphate ions. In some variations, the aqueous solvent consists essentially of water. In some embodiments, the chlorite formulations consist essentially of chlorite, water, sodium, and phosphate, and are substantially free of chlorate. In some embodiments, the chlorite formulations consist essentially of chlorite, water, sodium, and phosphate, and are substantially free of chlorate, and further include a pharmaceutically acceptable diluent. In some embodiments, the sodium and phosphate are provided in whole or in part in monosodium phosphate or disodium phosphate. In some embodiments, the pharmaceutically acceptable diluent is saline solution.

[0093] In some embodiments, the chlorite formulations described herein contain about 10% by weight or less of by-products or impurities present in commercially available technical grade chlorite.Non-limiting examples of by-products or impurities present in commercially available technical grade chlorite include chlorate, sulfate, chlorine dioxide, chloride, sodium bicarbonate, and sodium carbonate. In some embodiments, the chlorite formulations described herein contain no more than about 15% by weight, no more than about 12% by weight, no more than about 10% by weight, no more than about 9% by weight, no more than about 8% by weight, no more than about 7% by weight, no more than about 6% by weight, no more than about 5% by weight, no more than about 4% by weight, no more than about 3% by weight, no more than about 2% by weight, no more than about 1% by weight, no more than about 0.5% by weight, no more than about 0.3% by weight, no more than about 0.1% by weight, about 0.1 to about 5% by weight, about 5 to about 10% by weight, or about 10 to about 15% by weight of one or more degradation products or impurities present in commercially available technical grade chlorite, including but not limited to one or more of chlorate or sulfate. In some embodiments, the chlorite formulations described herein contain no more than about 0.5% by weight of one or more degradation products or impurities present in commercially available technical grade chlorite, including but not limited to one or more of chlorate or sulfate. In some embodiments, the chlorite formulations described herein contain about 5% by weight or less of decomposition products or impurities present in commercially available technical grade chlorite, including but not limited to one or more of chlorate or sulfate.In some embodiments, the chlorite formulations described herein are substantially free of decomposition products or impurities present in commercially available technical grade chlorite, including but not limited to chlorate or sulfate.

[0094] In some embodiments, the formulations described herein are less toxic to subjects at the same chlorite concentration than previously reported chlorite formulations when administered by at least one or more than one of the administration routes described herein, including but not limited to non-local, systemic, parenteral, or intravenous administration.In some embodiments, the toxicity of the chlorite formulation is analyzed for toxicity using in vivo or in vitro toxicity assays, including well-known toxicity assays.In some embodiments, the chlorite formulation is analyzed for toxicity using non-specific in vitro toxicity assays.

[0095] In another variation, toxicity is measured according to various response indicators of toxicity in a subject after administration of the chlorite formulation described herein compared to administration of other commercially available chlorite formulations.In some variations, toxicity is measured compared to systemic administration of chlorite formulated as WF10.In another variation, toxicity is measured compared to intravenous administration of chlorite formulated as WF10 to a subject.In some variations, toxicity is measured after administration to a mammalian subject, including but not limited to a human subject.In some variations, toxicity is measured as one or more of the following irritation to the surface to which the chlorite formulation is exposed, including but not limited to gastrointestinal tract, nausea, vomiting, diarrhea, abdominal pain, hemolysis, methemoglobinemia, cyanosis, anuria, coma, convulsions, liver damage, kidney damage, anorexia, or weight loss.In some variations, toxicity is measured as one or more of the following asthenia, pain at injection site, headache, rhinitis, or diarrhea. In another variation, toxicity is measured as anemia. In some variations, toxicity is measured as asthenia. In some variations, toxicity is measured as injection site reactions. In some variations, toxicity is measured as injection site pain.

[0096] III. Methods for Adjusting the pH of pH-Sensitive Formulations Various methods can be used to adjust the pH of the formulation and pharmaceutical preparation that includes chlorite.It is intended that the method described herein can be used to produce the formulation or pharmaceutical preparation described herein for use in the present disclosure.However, the formulation and pharmaceutical preparation described herein can also be produced by other methods, and the formulation and pharmaceutical preparation described herein is not limited to those produced by the method described herein.

[0097] Some compounds or formulations are sensitive to high local acidity or alkalinity and require a suitable method to adjust the pH of such compounds or formulations. Preferred pH adjusters or pH adjusting compounds are weak acids or weak bases with 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, phosphate buffers with a pKa of about 4 to about 9 well known in the art, such as monobasic phosphates, or monosodium phosphate and / or disodium phosphate, and lower alkanoic acids, such as acetic acid or propionic acid. In some embodiments, the pH of an acidity-sensitive formulation is lowered to about 7 to about 11.5 using a pH adjusting compound that does not expose the formulation to acidity, including but not limited to high local acidity in the area surrounding the pH adjusting compound. In some embodiments, the pH of the acidity sensitive formulation is lowered to about 7 to about 10 using a pH adjusting compound that does not expose the formulation to high acidity, including but not limited to, high local acidity in the area surrounding the pH adjusting compound. In some embodiments, the pH of the acidity sensitive formulation is lowered to about 7 to about 9.5 using a pH adjusting compound that does not expose the formulation to high acidity, including but not limited to, high local acidity in the area surrounding the pH adjusting compound. In some embodiments, the pH of the acidity sensitive formulation is lowered to about 7 to about 9.0 using a pH adjusting compound that does not expose the formulation to high acidity, including but not limited to, high local acidity in the area surrounding the pH adjusting compound. In some embodiments, the pH of the acidity sensitive formulation is lowered to about 7 to about 8.5 using a pH adjusting compound that does not expose the formulation to high acidity, including but not limited to, high local acidity in the area surrounding the pH adjusting compound. In some embodiments, the pH of an acidity-sensitive formulation is lowered to about 7.1 to about 7.7 using a pH adjusting compound that does not expose the formulation to high acidity, including, but not limited to, high local acidity in the area surrounding the pH adjusting compound.

[0098] "High local acidity" as used herein refers to the pKa of one or more molecules local to the chlorite molecule, as opposed to the overall acidity of the solution, which can be measured, for example, using a pH meter.To determine whether a pH adjuster subjects chlorite to high local acidity, the pKa of the pH adjuster can be determined, for example, using CRC Handbook of Chemistry and Physics (86th Edition, David R. Lideed., CRC Press, 2005).

[0099] It has been difficult to reduce the pH of chlorite formulations because many pH adjusters expose the compound or formulation to high acidity in the localized area of ​​the molecule of the pH adjuster compound.In the presence of high local acidity, some non-chlorite compounds, such as chlorate and / or chlorine dioxide, are generated.See, for example, Ullmann's Encyclopedia of Industrial Chemistry, Vol. A6, Ed.Wolfgang Gerhartz, 5th Ed. (1986), which is incorporated herein by reference in its entirety.Such decomposition products may be undesirable in formulations for parenteral or systemic administration to physiological systems, for example, because they are not inactive in physiological systems.Some such decomposition products cause toxicity, including but not limited to, non-specific toxicity, as described herein.

[0100] Unless otherwise clear from the context, the pH of any of the formulations or pharmaceutical preparations described herein may be adjusted using the methods described herein.

[0101] In some variations, the activity of the therapeutic agent, including but not limited to chlorite, is reduced by exposure to high local acidity. "Decreased activity" as used herein refers to the activity of the therapeutic agent that is qualitatively or quantitatively inferior to that of the therapeutic agent before exposure to high local acidity. As an example, the altered activity that is qualitatively or quantitatively inferior to that of the therapeutic agent before exposure to high local acidity will be less effective in wound healing or less effective in treating one or more of the diseases or conditions described herein. In some variations, the altered activity is at least about 3% or more lower than the activity of the therapeutic agent before exposure to high local acidity, at least about 5% or more lower, at least about 10% or more lower, at least about 15% or more lower, at least about 20% or more lower, or at least about 25% or more lower. In some variations, the altered activity is at least about 5% or more lower than the activity of the therapeutic agent before exposure to high local acidity.

[0102] In some embodiments, the pH of the chlorite formulation is adjusted to any one or more of the pH levels described in the formulations section or elsewhere herein. In some embodiments, the pH of the described chlorite formulation is about 7 to about 11.5. In some embodiments, the method adjusts the pH of the chlorite-containing formulation to about 7 to about 11, about 7 to about 10.5, about 7 to about 10, about 7 to about 9.5, about 7 to about 9, about 7 to about 8.5, about 7 to about 8.0, about 7 to about 7.5, about 7.5 to about 8, about 7.5 to about 8.5, about 7 to about 8, about 7.1 to about 7.7, about 7.2 to about 7.6, about 7.3 to about 7.5, about 8 to about 9, about 8 to about 8.5, about 8.5 to about 9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8.0, about 8.1, about 8.2, about 8.3, about 8.4, about 8.5, about 8.6, about 8.7, about 8.8, or about 8.9. In some embodiments, the method comprises reducing the pH of the formulation comprising chlorite to about 7 to about 8.5. In some embodiments, the method comprises reducing the pH of the formulation comprising chlorite to about 7 to about 8.0. In some embodiments, the method comprises reducing the pH of the formulation comprising chlorite to about 7.1 to about 7.7. In some embodiments, the method includes lowering the pH of the chlorite-containing formulation to about 7.4.

[0103] In one non-limiting example, the pH of the mixture containing chlorite is adjusted using a pH adjuster that does not subject chlorite to a local pH below 7 when exposed to the mixture containing chlorite. In some embodiments, the pH adjuster is monosodium phosphate, disodium phosphate, or a mixture thereof. In some embodiments, monosodium phosphate and / or disodium phosphate are used as solids or in solution. In some embodiments, the pH adjuster is acetic acid.

[0104] In some embodiments, the pH of chlorite is adjusted by adding chlorite or the aqueous mixture containing chlorite to the solution containing buffer.In some embodiments, the pH of chlorite is adjusted by adding chlorite or the aqueous mixture containing chlorite to phosphate buffer solution.

[0105] In some variations, the pH of the chlorite solution or mixture is adjusted using one or more pH adjusters, and the resulting solution or mixture is analyzed for the presence of chlorite decomposition products, including but not limited to decomposition products generated by high local acidity. In some variations, the pH of the chlorite solution or mixture is adjusted using a pH adjuster, such as acetic acid, monosodium phosphate, and / or disodium phosphate, and the resulting solution or mixture is analyzed for the presence of chlorate or chlorine dioxide.

[0106] In some embodiments, the resulting solution or mixture is analyzed for degradation products using well-known analytical methods, e.g., HPLC, mass spectrometry, etc. In some embodiments, the resulting solution or mixture is analyzed for degradation products using toxicity assays, including well-known toxicity assays. In some embodiments, the resulting solution or mixture is analyzed for impurities using non-specific toxicity assays.

[0107] In some embodiments, the pH of the chlorite formulation is adjusted after the chlorite purification step. In some embodiments, the pH of the chlorite formulation is adjusted to about 7 to about 11.5 without the generation of chlorite degradation products that are a result of high local acidity. In some embodiments, the pH of the chlorite formulation is adjusted to about 7 to about 8.0 without the generation of chlorite degradation products that are a result of high local acidity. In some embodiments, the pH of the chlorite formulation is adjusted to any of about 7 to about 11, about 7 to about 10.5, about 7 to about 10, about 7 to about 9.5, about 7 to about 9, about 7 to about 8.5, about 7 to about 8, about 7 to about 7.5, about 7.5 to about 8, about 7.5 to about 8.5, about 7 to about 8, about 8 to about 9, about 8 to about 8.5, or about 8.5 to about 9 without the generation of chlorite degradation products that are a result of high local acidity.

[0108] IV. Pharmaceutical Preparations Unless the context clearly indicates otherwise, any of the formulations described herein may be used in any of the pharmaceutical formulations described herein. In a preferred embodiment, the pharmaceutical composition may include (a) chlorite and (b) a pharma- ceutically acceptable excipient. The pharmaceutical composition may further include a pH adjuster. In some embodiments, the pH adjuster includes monosodium phosphate and / or disodium phosphate. The pH adjuster may include a phosphate buffer. The pH of the composition may be about 7.1 to about 7.7, e.g., 7.4. The formulation may have a low level of harmful chlorate, e.g., the weight ratio of chlorite:chlorate may be greater than 100:1.5, greater than 100:1, greater than 99:1, greater than 97:1, or may be substantially free of chlorate. Such formulations may be formulated for intravenous administration.

[0109] The pharmaceutical formulations described herein may be suitable for administration to a subject. "Suitable for administration to a subject" means that the pharmaceutical formulation, when obtained from a freshly opened bottle and administered via the desired route, does not cause adverse side effects above clinically acceptable levels.

[0110] The formulation or pharmaceutical formulation described herein may further comprise a saline solution.Saline solution, as used herein, refers to a physiologically acceptable solution having a physiologically acceptable level of sodium chloride.In some embodiments, the saline solution is isotonic.

[0111] The chlorite formulation for use in the present disclosure can be a pharma- ceutically acceptable chlorite formulation that contains one or more pharma-ceutically acceptable excipients.Excipients, as used herein, refer to any non-chlorite, non-water, non-saline element of pharmaceutical formulation.Excipients include, but are not limited to, carriers, adjuvants, diluents, stabilizers, wetting agents, emulsifiers, buffers, preservatives, flavorings, inactive ingredients, gel preparations, erodible and non-erodible polymers, microspheres, liposomes, etc., which are known to those skilled in the art and further described herein, and include combinations of the above. In some embodiments, the weight percentage of excipients per total volume of the formulation or pharmaceutical preparation is about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, about 0.5%, about 0.4%, about 0.3%, about 0.2%, about 0.1%, or about 0.05% or less. In some embodiments, the weight percentage of excipients per total volume of the formulation or pharmaceutical preparation is about 1% or less. In some embodiments, the weight percentage of excipients per total volume of the formulation or pharmaceutical preparation is about 3% or less.

[0112] The following is a non-limiting and non-exhaustive list of excipients commonly used in the pharmaceutical field. These excipients are commonly used in various types of formulations, including those formulated for intravenous, oral, intramuscular, or parenteral administration. Given the reactivity of chlorite, some of the excipients listed below are likely to be inappropriate for a given pharmaceutical formulation. Whether a particular excipient is inappropriate for a given pharmaceutical formulation may depend on the amount of excipient added to the pharmaceutical formulation. Before adding one or more of any excipients, including but not limited to the excipients described herein, to a pharmaceutical formulation of chlorite, it is important to consider the excipient's reactivity with chlorite. Some organic molecules commonly used as excipients react with chlorite in such a way that the excipient is changed, including but not limited to changes that result in an increase in the toxicity of the pharmaceutical formulation before the excipient is exposed to chlorite. In some embodiments, the pharmaceutical formulations described herein include one or more pharma- ceutically acceptable excipients that do not react with chlorite. Preferably, the pharmaceutical formulations described herein include one or more pharma- ceutically acceptable excipients that do not decrease the therapeutic efficacy of the pharmaceutical formulation compared to before exposure to the excipient.

[0113] The chlorite formulations described herein may include one or more pharma- ceutically acceptable excipients that do not produce one or more of the harmful non-chlorite elements of other commercially available chlorite formulations.In some embodiments, the chlorite formulations described herein include excipients and are substantially free of one or more of the harmful non-chlorite elements of other commercially available chlorite formulations.The chlorite formulations described herein may include excipients and may be substantially free of one or more of the degradation products or impurities of other commercially available chlorite formulations described herein.

[0114] Chlorite formulations may contain stabilizers.Stabilizers include, but are not limited to, agents that will (1) improve the compatibility of excipients with containers, including glass bottles, or encapsulating materials such as gelatin, (2) improve the stability of chlorite (e.g., prevent degradation), (3) improve formulation stability, or any combination thereof.Stabilizers may be selected from, for example, fatty acids, fatty alcohols, alcohols, long-chain fatty acid esters, long-chain ethers, hydrophilic derivatives of fatty acids, polyvinylpyrrolidone, polyvinyl ethers, polyvinyl alcohols, hydrocarbons, hydrophobic polymers, hygroscopic polymers, and combinations thereof.Amide analogs of stabilizers may also be used. The stabilizer selected may change the hydrophobicity of the formulation (e.g., oleic acid, wax), or improve the mixing of the various components of the formulation (e.g., ethanol), control the moisture level of the formulation (e.g., PVP or polyvinylpyrrolidone), control phase mobility (substances with melting points higher than room temperature, e.g., long chain fatty acids, alcohols, esters, ethers, amides, etc., or mixtures thereof, wax), and / or improve the compatibility of the formulation with the encapsulating material (e.g., oleic acid, wax). Some of these stabilizers may be used as solvents / co-solvents (e.g., ethanol). The stabilizer may be present in an amount sufficient to inhibit the decomposition of chlorite.

[0115] The formulations described herein may contain one or more of a gelling agent or a release-modifying agent.

[0116] The formulations described herein may contain one or more adjuvants suitable for the indicated route of administration.Again, before adding any excipients to the formulations described herein, the reactivity of chlorite should be considered as to whether the resulting pharmaceutical formulation is suitable for administration via the desired route of administration.Adjuvants that can be mixed with the therapeutic agent include, but are not limited to, lactose, sucrose, starch powder, cellulose esters of alkanoic acid, stearic acid, talc, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphate and sulfate, acacia, gelatin, sodium alginate, polyvinylpyrrolidone, and / or polyvinyl alcohol.When a solubilized formulation is required, the therapeutic agent can be in a solvent, including, but not limited to, polyethylene glycols of various molecular weights, propylene glycols of various molecular weights, carboxymethylcellulose colloidal solution, methanol, ethanol, DMSO, corn oil, peanut oil, cottonseed oil, sesame oil, tragacanth gum, and / or various buffers. Other adjuvants and modes of administration are well known in the pharmaceutical field and can be used in the implementation of the methods and formulations described herein.Carriers or diluents can include time-delay materials, such as glyceryl monostearate or glyceryl distearate alone or in combination with wax, or other materials well known in the art.Formulations for use as described herein can also include gel formulations, erodible and non-erodible polymers, microspheres, and liposomes.

[0117] Additives and diluents commonly used in the pharmaceutical field may be added to pharmaceutical compositions and liquid formulations as necessary. These include thickeners, granulating agents, dispersing agents, flavoring agents, sweeteners, coloring agents, and stabilizers including pH stabilizers, other excipients, antioxidants (e.g., tocopherol, BHA, BHT, TBHQ, tocopherol acetate, ascorbyl palmitate, ascorbyl gallate, etc.), preservatives (e.g., parabens), etc. Exemplary preservatives include, but are not limited to, benzyl alcohol, ethyl alcohol, benzalkonium chloride, phenol, chlorobutanol, etc. Some antioxidants provide oxygen or peroxide inhibitors and may be used in the formulations described herein, including, but not limited to, butylated hydroxytoluene, butylated hydroxyanisole, propyl gallate, ascorbyl palmitate, a-tocopherol, etc. Thickening agents, such as lecithin, hydroxypropylcellulose, aluminum stearate, and the like, can be used if desired, for example, to improve one or more qualities of the formulation, such as texture.

[0118] In some variations, the chlorite formulations for use in the present disclosure are sterile. Sterilization can be carried out by any method that is compatible with chlorite. In some embodiments, sterilization is by a method that does not generate substantial amounts of decomposition products of chlorite. In some embodiments, sterilization is by a method that does not cause structural changes of chlorite. In some embodiments, the formulations described herein are sterile pharmaceutical formulations for parenteral or intravenous administration. In some embodiments, the chlorite formulations described herein are sterile filtered, for example, through a 0.22 micron sterile filter.

[0119] The formulation or pharmaceutical formulation may be sterile filterable. In some embodiments, the chlorite formulations described herein are formulated for administration by one or more of the administration routes described herein. A formulation that is "formulated for administration" by a specified administration route, as used herein, is a formulation that does not contain pharmaceutical excipients that are considered inappropriate for the administration route by those skilled in the relevant art. As an example, a formulation that is suitable for intravenous administration will not contain the excipients or carriers of toothpaste intended for topical administration, in which case the excipients or carriers are considered inappropriate for the specified administration route by those skilled in the relevant art.

[0120] Any form of chlorite-containing drug disclosed herein can be provided in any suitable formulation, which can be selected according to the desired route of administration disclosed herein.In one embodiment, the drug product formulation comprises purified sodium chlorite, which may include a certain amount of water content, a buffer, such as disodium hydrogen phosphate, and sterile water for injection (USP) as a vehicle.In one embodiment, the amount of purified sodium chlorite is about 5.6mg / mL (including a batch factor that reflects the water content of the batch), the amount of disodium hydrogen phosphate is about 0.107mg / mL, and includes sterile water to make up to a volume of 1mL.In certain embodiments, the formulation according to the present disclosure consists essentially of purified sodium chlorite, a buffer, and sterile water for injection (USP) as a vehicle.In certain embodiments, the formulated drug product is stable at 25°C / 60% relative humidity and / or 40°C / 75% relative humidity conditions for up to 3 months.

[0121] Treatment Method The exemplary method of patient selection and the method of treatment with pharmaceutical compositions comprising sodium chlorite are disclosed herein.The factors that identify a patient as a member of the ALS patient subpopulation that is likely to be responsive to treatment with pharmaceutical compositions comprising sodium chlorite include patient age, elevated plasma CRP level, or time since the onset of ALS symptoms, and combinations thereof.

[0122] Also disclosed herein is a method for treating early-onset ALS. In an exemplary embodiment, the method for treating early-onset ALS includes patients with stable disease who have elevated C-reactive protein (CRP) levels of at least 1.13 mg / L or more.

[0123] Also disclosed herein is a method of treating endometriosis. In an exemplary embodiment, the method of treating endometriosis comprises administering chlorite to a subject.

[0124] In one aspect, the method of treating ALS in a subject described herein may include administering to the subject, in the active drug arm, chlorite at a dosage of 2 mg / kg chlorite (in the form of formulated sodium chlorite) for 5 days in the first month, followed by 3 consecutive days per month for the following 5 months, in a drug infusion over 60 minutes, where the subject is a member of the target ALS patient population. In some embodiments, the method includes administering to the subject chlorite at a dosage of a pharmaceutical composition comprising 1 mg / kg sodium chlorite. The patient may be a member of the target ALS patient population based on an elevated plasma C-reactive protein (CRP) level above 1.13 mg / L and a patient age of 40 to 65 years. In some embodiments, the patient may be a member of a target ALS patient population based on highly elevated plasma C-reactive protein (CRP) levels (e.g., greater than 3 mg / L), time since onset of ALS symptoms (e.g., greater than 12 months), age (e.g., 40-65 years), or a combination thereof.

[0125] Embodiments described herein include a method of treating a subject having ALS with chlorite, comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has at least 1.13 mg / L or greater of CRP, where if the plasma sample has at least 1.13 mg / L or greater, the subject has an elevated plasma CRP level; and b) administering chlorite to the subject if the subject has an elevated plasma CRP level, where the subject is between 40 and 65 years of age.Non-limiting plasma CRP levels include at least 1.1 mg / L or greater, at least 1.13 mg / L or greater, at least 1.15 mg / L or greater, at least 1.2 mg / L or greater, at least 1.3 mg / L or greater, at least 1.4 mg / L or greater, at least 1.5 mg / L or greater, at least 1.6 mg / L or greater, at least 1.7 mg / L or greater, at least 1.8 mg / L or greater, at least 1.9 mg / L or greater, at least 2.1 mg / L or greater, at least 2.2 mg / L or greater, at least 2.3 mg / L or greater, at least 2.4 mg / L or greater, at least 2.5 mg / L or greater, at least 2.6 mg / L or greater, at least 2.7 mg / L or greater, at least 2.8 mg / L or greater, at least 2.9 mg / L or greater and at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L or greater.Non-limiting plasma CRP levels include levels that are 30mg / L or less or more, 29mg / L or less or more, 28mg / L or less or more, 27mg / L or less or more, 26mg / L or less or more, 25mg / L or less or more, 24mg / L or less or more, 23mg / L or less or more, 22mg / L or less or more, 21mg / L or less or more, 20mg / L or less or more, 15mg / L or less or more, or 10mg / L or less or more. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reaction, and high sensitivity near-infrared particle immunoassay rate method. In some methods, the subject has experienced ALS symptoms for at least 12 months or more, or at least 18 months or more, prior to administration of chlorite. For example, the subject has been experiencing symptoms of ALS for at least 12 months or longer, at least 13 months or longer, at least 14 months or longer, at least 15 months or longer, at least 16 months or longer, at least 17 months or longer, at least 18 months or longer, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, at least 30 months or longer, or at least 33 months or longer.Symptoms of ALS include those described herein, including, but not limited to, muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, poor fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, poor coordination, pain, fatigue, difficulty walking, increased clumsiness of movement, and combinations of two or more of these.Determining the length of time that the subject has been experiencing symptoms of ALS may include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject regarding when they first began experiencing symptoms.In an exemplary embodiment, the method is carried out as described in Examples 1-4.

[0126] The embodiments described herein also include combination therapy with one or more neurotrophic factors. In some cases, the neurotrophic factors include neurotrophins, glial cell line-derived neurotrophic factor family ligands (GFLs), or neuropoietic cytokines. In some cases, the neurotrophic factors include brain-derived neurotrophic factor (BDNF). In some cases, BDNF promotes thymocyte survival. In some cases, BDNF promotes dorsal root ganglion neuron survival. In some cases, the neurotrophic factors include nerve growth factor (NGF). In some cases, NGF promotes myelination and neuronal differentiation, possibly using the high affinity receptor TrkA. In some cases, the neurotrophic factors include neurotrophin-3 or neurotrophin-4. In some cases, the neurotrophic factors include ciliary neurotrophic factor, glial cell line-derived neurotrophic factor (GDNF), artemin, neurturin, or persephin. In some cases, the neurotrophic factor comprises an ephrin: A1, A2, A3, A4, A5, B1, B2, or B3. In some cases, the neurotrophic factor comprises an epidermal growth factor, a neuregulin, a transforming growth factor alpha (TGFα), or a transforming growth factor beta (TGFβ).

[0127] In one aspect, described herein is a method of treating ALS in a subject, comprising administering chlorite to the subject, wherein the subject is between 40 and 65 years old. Also described herein is a method of treating a subject with ALS with chlorite, comprising determining whether the subject is between 40 and 65 years old, and administering chlorite to the subject if the subject is between 40 and 65 years old. In some embodiments, the method comprises not treating the subject if the subject is not between 40 and 65 years old. In some methods, the subject has been experiencing symptoms of ALS for at least 12 months or longer, or at least 18 months or longer, prior to administration of chlorite. For example, the subject has been experiencing symptoms of ALS for at least 12 months or longer, at least 13 months or longer, at least 14 months or longer, at least 15 months or longer, at least 16 months or longer, at least 17 months or longer, at least 18 months or longer, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, at least 30 months or longer, or at least 33 months or longer.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.The step of determining the length of time that the subject has experienced symptoms of ALS can include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject regarding when he or she first began experiencing symptoms of ALS.The diagnosis of ALS can be achieved based on electromyogram (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy.In some methods, the sample from the subject has a level of CRP of at least 3mg / L or more. At least 3 mg / L or greater includes, without limitation, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L. A subject's plasma CRP level may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, the subject's plasma CRP level may be between 3 mg / L and 10 mg / L, 3.1 mg / L and 10 mg / L, 3.2 mg / L and 10 mg / L, 3.3 mg / L and 10 mg / L, 3.4 mg / L and 10 mg / L, 3.5 mg / L and 10 mg / L, 3.6 mg / L and 10 mg / L, 3.7 mg / L and 10 mg / L, 3.8 mg / L and 10 mg / L, 3.9 mg / L and 10 mg / L, / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~10mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~ 8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4m The plasma level may be 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods. In an exemplary embodiment, the method is performed as described in Examples 1-4.

[0128] In one aspect, described herein is a method of treating ALS in a subject, comprising administering chlorite to the subject, wherein the subject is between 40 and 65 years of age. In another aspect, the method can comprise determining whether the subject has an elevated plasma CRP level as indicated by a plasma sample from the subject having at least 3 mg / L or greater CRP, and administering chlorite to the subject, wherein the subject is between 40 and 65 years of age. In another aspect, the method can comprise determining whether the subject has experienced symptoms of ALS for at least 12 months or longer, and administering chlorite to the subject, wherein the subject is between 40 and 65 years of age. In a further aspect, the method may include determining whether a subject has an elevated plasma C-reactive protein (CRP) level as indicated by a plasma sample from the subject having at least 3 mg / L or greater CRP, determining whether the subject has been experiencing symptoms of ALS for at least 12 months or longer, and administering chlorite to the subject, wherein the subject is between 40 and 65 years of age.

[0129] In some embodiments, the subject is between 40 and 65 years old, e.g., between 45 and 65 years old, between 50 and 65 years old, between 55 and 65 years old, between 60 and 65 years old, between 45 and 60 years old, between 45 and 55 years old, or between 45 and 50 years old. In some embodiments, the subject is up to 65 years old, e.g., 20-65 years old, 25-65 years old, 30-65 years old, 35-65 years old, 40-65 years old, 45-65 years old, 50-65 years old, 55-65 years old, 60-65 years old, 20-60 years old, 20-55 years old, 20-50 years old, 20-45 years old, 20-40 years old, 20-35 years old, 20-30 years old, 20-25 years old, 25-65 years old, 25-60 years old, 25-55 years old, 25-50 years old, 25-45 years old, 25-40 years old, 25-35 years old, 25-30 years old, 30-45 years old, 30-55 years old, 30-65 years old, 30-75 years old, 30-80 years old, 30-90 years old, 30-100 years old, 30-120 years old, 30-140 years old, 30-160 years old, 30-180 years old, 30-200 years old, 30-220 years old, 30-240 years old, 30-260 years old, 30-280 years old, 30-320 years old, 30-360 years old, 30-380 years old, 30-40 years old, 30-42 years old, 30-42 years old, 30-52 years old, 30-52 years old, 30-52 years old, 30-60 years old, 30-60 years old, 30-70 years old, 0-65 years, 30-60 years, 30-55 years, 30-50 years, 30-45 years, 30-40 years, 30-35 years, 35-65 years, 35-60 years, 35-55 years, 35-50 years, 35-45 years, 35-40 years, 40-65 years, 40-60 years, 40-55 years, 40-50 years, 40-45 years, 45-65 years, 45-60 years, 45-55 years, 45-50 years, 50-65 years, 50-60 years, 50-55 years, 55-65 years, 55-60 years, or 60-65 years.

[0130] Also described herein is a method of treating a subject having ALS with chlorite, the method comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has at least 3 mg / L or greater CRP, where if the plasma sample has at least 3 mg / L or greater, the subject has an elevated plasma CRP level; and b) administering chlorite to the subject if the subject has an elevated plasma CRP level, where the subject is between 40 and 65 years of age. Non-limiting elevated plasma CRP levels include levels of at least 3 mg / L or greater, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L or greater. Elevated plasma CRP levels may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, elevated plasma CRP levels are 3mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.2mg / L to 10mg / L, 3.3mg / L to 10mg / L, 3.4mg / L to 10mg / L, 3.5mg / L to 10mg / L, 3.6mg / L to 10mg / L, 3.7mg / L to 10mg / L, 3.8mg / L to 10mg / L, 3.9 ...1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to g / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~1 0mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4mg The plasma level may be 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods. In an exemplary embodiment, the method is performed as described in Examples 1-4.

[0131] Also described herein is a method of treating a subject having ALS with chlorite, the method comprising: a) determining the length of time that the subject has been experiencing symptoms of ALS for at least 12 months or longer; and b) administering chlorite to the subject, wherein the subject is between 40 and 65 years of age. Non-limiting examples of ALS symptom duration include a subject experiencing ALS symptoms for at least 12 months or longer, at least 13 months or longer, at least 14 months or longer, at least 15 months or longer, at least 16 months or longer, at least 17 months or longer, at least 18 months or longer, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, or at least 30 months or longer.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.The step of determining the length of time the subject has been experiencing symptoms of ALS may include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS.

[0132] Also described herein is a method of treating a subject having ALS with chlorite, comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level, as indicated by a plasma sample from the subject having at least 3 mg / L or greater CRP; b) determining the length of time that the subject has been experiencing symptoms of ALS for at least 12 months or longer; and c) administering chlorite to the subject, wherein the subject is between 40 and 65 years of age. Also described herein is a method of treating a subject having ALS with chlorite, the method comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has at least 3 mg / L or greater CRP, where if the plasma sample has at least 3 mg / L or greater, the subject has an elevated plasma CRP level; and b) administering chlorite to the subject if the subject has an elevated plasma CRP level, where the subject is between 40 and 65 years of age.Non-limiting elevated plasma CRP levels include levels of at least 3 mg / L or greater, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L or greater. Elevated plasma CRP levels may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, elevated plasma CRP levels are 3mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.2mg / L to 10mg / L, 3.3mg / L to 10mg / L, 3.4mg / L to 10mg / L, 3.5mg / L to 10mg / L, 3.6mg / L to 10mg / L, 3.7mg / L to 10mg / L, 3.8mg / L to 10mg / L, 3.9 ...1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to g / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~1 0mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4mg The plasma level may be 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods.Non-limiting examples of ALS symptom duration include a subject experiencing ALS symptoms for at least 12 months or longer, at least 13 months or longer, at least 14 months or longer, at least 15 months or longer, at least 16 months or longer, at least 17 months or longer, at least 18 months or longer, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, or at least 30 months or longer.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.The step of determining the length of time the subject has been experiencing symptoms of ALS may include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS.

[0133] In one aspect, a method of treating ALS in a subject is described herein, comprising administering chlorite to the subject, and the subject has elevated plasma CRP levels, as indicated by a plasma sample from the subject having at least 3 mg / L or more CRP.Also described herein is a method of treating a subject with ALS with chlorite, comprising: a) determining whether the subject has elevated plasma CRP levels by performing or performing an assay on the plasma sample to determine whether the plasma sample from the subject has at least 3 mg / L or more CRP, and if the plasma sample has at least 3 mg / L or more, the subject has elevated plasma CRP levels; and b) administering chlorite to the subject if the subject has elevated plasma CRP levels. Non-limiting elevated plasma CRP levels include levels of at least 3 mg / L or greater, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L or greater. Elevated plasma CRP levels may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, elevated plasma CRP levels are 3mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.2mg / L to 10mg / L, 3.3mg / L to 10mg / L, 3.4mg / L to 10mg / L, 3.5mg / L to 10mg / L, 3.6mg / L to 10mg / L, 3.7mg / L to 10mg / L, 3.8mg / L to 10mg / L, 3.9 ...1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to g / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~1 0mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4mg g / L to 8 mg / L, 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods of determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods. In exemplary embodiments, the method is performed as described in Examples 1-4. In some methods, the subject may have been experiencing symptoms of ALS for at least 12 months or longer.For example, the subject has been experiencing symptoms of ALS for at least 12 months or longer, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, or at least 30 months or longer.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.Determining the length of time the subject has experienced symptoms of ALS may include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS. A diagnosis of ALS may be achieved based on electromyography (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy. In some methods, the subject is between 40 and 65 years old.

[0134] In one aspect, described herein is a method for treating ALS in a subject, comprising administering chlorite to the subject, wherein the subject has experienced symptoms of ALS for at least 12 months or longer, or at least 18 months or longer, prior to administration of chlorite.Also described herein is a method for treating a subject with ALS with chlorite, comprising a) determining the length of time the subject has experienced symptoms of ALS, and b) administering chlorite to the subject if the subject has experienced symptoms of ALS for at least 12 months or longer, or at least 18 months or longer. For example, the subject has been experiencing symptoms of ALS for at least 12 months or longer, at least 13 months or longer, at least 14 months or longer, at least 15 months or longer, at least 16 months or longer, at least 17 months or longer, at least 18 months or longer, at least 19 months or longer, at least 20 months or longer, at least 21 months or longer, at least 22 months or longer, at least 23 months or longer, at least 24 months or longer, at least 25 months or longer, at least 26 months or longer, at least 27 months or longer, at least 28 months or longer, at least 29 months or longer, or at least 30 months or longer.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.The step of determining the length of time that the subject has experienced symptoms of ALS can include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject regarding when he or she first began experiencing symptoms of ALS.The diagnosis of ALS can be achieved based on electromyogram (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy.In some methods, the sample from the subject has a level of CRP of at least 3mg / L or more. At least 3 mg / L or greater includes, without limitation, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L. A subject's plasma CRP level may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, the subject's plasma CRP level may be between 3 mg / L and 10 mg / L, 3.1 mg / L and 10 mg / L, 3.2 mg / L and 10 mg / L, 3.3 mg / L and 10 mg / L, 3.4 mg / L and 10 mg / L, 3.5 mg / L and 10 mg / L, 3.6 mg / L and 10 mg / L, 3.7 mg / L and 10 mg / L, 3.8 mg / L and 10 mg / L, 3.9 mg / L and 10 mg / L, / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~10mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~ 8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4m The plasma level may be 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods. In exemplary embodiments, the method is performed as described in Examples 1-4. In some methods, the subject is between 40 and 65 years old.

[0135] In one aspect, described herein is a method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, where the subject i) has elevated plasma C-reactive protein (CRP) levels, as indicated by a plasma sample from the subject having at least 3 mg / L or greater CRP, and ii) has been experiencing symptoms of ALS for at least 12 months or more, or at least 18 months or more, prior to administration of chlorite. Also described herein is a method of treating a subject having ALS with chlorite, the method comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has at least 3 mg / L or greater CRP, where if the plasma sample has at least 3 mg / L or greater, the subject has an elevated plasma CRP level; b) determining the length of time the subject has been experiencing symptoms of ALS; and c) administering chlorite to the subject if the subject has an elevated plasma CRP level and has been experiencing symptoms of ALS for at least 12 months or longer, or at least 18 months or longer.Non-limiting elevated plasma CRP levels include levels of at least 3 mg / L or greater, at least 3.1 mg / L or greater, at least 3.2 mg / L or greater, at least 3.3 mg / L or greater, at least 3.4 mg / L or greater, at least 3.5 mg / L or greater, at least 3.6 mg / L or greater, at least 3.7 mg / L or greater, at least 3.8 mg / L or greater, at least 3.9 mg / L or greater, at least 4 mg / L or greater, at least 4.1 mg / L or greater, at least 4.2 mg / L or greater, at least 4.3 mg / L or greater, at least 4.4 mg / L or greater, at least 4.5 mg / L or greater, at least 4.6 mg / L or greater, at least 4.7 mg / L or greater, at least 4.8 mg / L or greater, at least 4.9 mg / L or greater, or at least 5 mg / L or greater. Elevated plasma CRP levels may be as high as 5, 6, 7, 8, 9, or 10 mg / L.For example, elevated plasma CRP levels are 3mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.2mg / L to 10mg / L, 3.3mg / L to 10mg / L, 3.4mg / L to 10mg / L, 3.5mg / L to 10mg / L, 3.6mg / L to 10mg / L, 3.7mg / L to 10mg / L, 3.8mg / L to 10mg / L, 3.9 ...1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to 10mg / L, 3.1mg / L to g / L~10mg / L, 4mg / L~10mg / L, 4.1mg / L~10mg / L, 4.2mg / L~10mg / L, 4.3mg / L~10mg / L, 4.4mg / L~1 0mg / L, 4.5mg / L~10mg / L, 4.6mg / L~10mg / L, 4.7mg / L~10mg / L, 4.8mg / L~10mg / L, 4.9mg / L~10mg / L, 5mg / L~10mg / L, 3mg / L~8mg / L, 3.1mg / L~8mg / L, 3.2mg / L~8mg / L, 3.3mg / L~8mg / L, 3.4mg / L~8mg / L, 3.5mg / L~8mg / L, 3.6mg / L~8mg / L, 3.7mg / L~8mg / L, 3.8mg / L~8mg / L, 3.9mg / L~8mg / L, 4mg The plasma level may be 4.1 mg / L to 8 mg / L, 4.2 mg / L to 8 mg / L, 4.3 mg / L to 8 mg / L, 4.4 mg / L to 8 mg / L, 4.5 mg / L to 8 mg / L, 4.6 mg / L to 8 mg / L, 4.7 mg / L to 8 mg / L, 4.8 mg / L to 8 mg / L, 4.9 mg / L to 8 mg / L, or 5 mg / L to 8 mg / L. Non-limiting methods for determining plasma levels in a sample include latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, and high sensitivity near-infrared particle immunoassay rate methods. In an exemplary embodiment, the method is performed as described in Examples 1-4.In some cases, at least 12 months or more includes at least 12 months or more, at least 13 months or more, at least 14 months or more, at least 15 months or more, at least 16 months or more, at least 17 months or more, at least 18 months or more, at least 19 months or more, at least 20 months or more, at least 21 months or more, at least 22 months or more, at least 23 months or more, at least 24 months or more, at least 25 months or more, at least 26 months or more, at least 27 months or more, at least 28 months or more, at least 29 months or more, or at least 30 months or more.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject may be 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months, months, 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months months-40 months, 18 months-30 months, 19 months-60 months, 19 months-50 months, 19 months-40 months, 19 months-30 months, 20 months-60 months, 20 months-50 months, 20 months-40 months, 20 months-30 months, 21 months-60 months, 21 months-50 months, 21 months-40 months, 21 months-30 months, 22 months-60 months, 22 months-50 months Have been experiencing ALS symptoms for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months. Symptoms of ALS include those described herein, including, without limitation, muscle weakness, muscle cramps, muscle spasms, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, and combinations of two or more of these.Determining the length of time the subject has experienced symptoms of ALS may include reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS. A diagnosis of ALS may be achieved based on electromyography (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy. In some methods, the subject is between 40 and 65 years old.

[0136] In some methods, the subject may have experienced symptoms of ALS for at least 12 months or longer, or at least 18 months or longer, and have an elevated plasma CRP level of at least 3.0 mg / L or greater, e.g., a CRP level of 3.0-10 mg / L for 12-24 months or 18-21 months from symptom onset, a CRP level of 3.0-5.0 mg / L for 12-24 months or 18-21 months from symptom onset, a CRP level of 3.0-4.0 mg / L for 12-24 months or 18-21 months from symptom onset, / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.1-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.2-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.3-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.3-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.4-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 3.5-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 3.6-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 3.7-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 3.8-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 3.9-5.0 mg / L; 12-24 months or 12-24 months or 18-21 months from symptom onset and a CRP level of 4-10 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.1-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.2-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.3-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.3-5.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.4-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.5-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.6-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.7-5.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.8-5.0 mg / L, or 12-24 months or 18-21 months from symptom onset and a CRP level of 4.9-5.0 mg / L. In some methods, the subject is between 40 and 65 years of age.

[0137] In some methods, the subject may have experienced symptoms of ALS for at least 21 months or longer and have an elevated plasma CRP level of at least 3.0 mg / L or greater, e.g., a CRP level of 3.0-10 mg / L at 21-36 months from symptom onset, a CRP level of 3.0-5.0 mg / L at 21-36 months from symptom onset, a CRP level of 3.0-4.0 mg / L at 21-36 months from symptom onset, a CRP level of 3.1-5.0 mg / L at 21-36 months from symptom onset, a CRP level of 3.1-5.0 mg / L at 21-36 months from symptom onset, or a CRP level of 3.0-4.0 mg / L at 21-36 months from symptom onset. CRP level of 3.2-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.3-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.3-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.4-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.5-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.6-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.7-5.0 mg / L for 21-36 months from symptom onset CRP level of 3.8-5.0 mg / L for 21-36 months from symptom onset, CRP level of 3.9-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4-10 mg / L for 21-36 months from symptom onset, CRP level of 4.1-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.2-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.3-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.4-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.5-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.6-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.7-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.8-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.9 ...9-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.1-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.2-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.3-5.0 mg / L for 21-36 months from symptom onset, CRP level of 4.4-5 A CRP level of 4.3-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.4-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.5-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.6-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.7-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.8-5.0 mg / L for 21-36 months from symptom onset and a CRP level of 4.9-5.0 mg / L for 21-36 months from symptom onset. In some methods, the subject is between 40 and 65 years of age.

[0138] In some methods, the subject may have experienced symptoms of ALS for at least 12 months or longer, or at least 18 months or longer, and have an elevated plasma CRP level of at least 4.0 mg / L or greater, e.g., a CRP level of 4.0-10 mg / L for 12-24 months or 18-21 months from symptom onset, a CRP level of 4.0-6.0 mg / L for 12-24 months or 18-21 months from symptom onset, a CRP level of 4.0-5.0 mg / L for 12-24 months or 18-21 months from symptom onset, or a CRP level of 4.0-6.0 mg / L for 12-24 months or 18-21 months from symptom onset, / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.1-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.2-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.3-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.3-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.4-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 4.5-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.6-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.7-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.8-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4.9-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 4. 12-24 months or 18-21 months from symptom onset and a CRP level of 4-10 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 5.1-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 5.2-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 5.3-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 5.3-6.0 mg / L; 12-24 months or 18-21 months from symptom onset and a CRP level of 5.4-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 5.5-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 5.6-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 5.7-6.0 mg / L, 12-24 months or 18-21 months from symptom onset and a CRP level of 5.8-6.0 mg / L, or 12-24 months or 18-21 months from symptom onset and a CRP level of 5.9-6.0 mg / L. In some methods, the subject is between 40 and 65 years old.

[0139] In some methods, the subject may have experienced symptoms of ALS for at least 18 months or longer and have an elevated plasma CRP level of at least 4.0 mg / L or greater, e.g., a CRP level of 4.0-10 mg / L at 21-36 months from symptom onset, a CRP level of 4.0-6.0 mg / L at 21-36 months from symptom onset, a CRP level of 4.0-5.0 mg / L at 21-36 months from symptom onset, a CRP level of 4.1-6.0 mg / L at 21-36 months from symptom onset, a CRP level of 4.1-6.0 mg / L at 21-36 months from symptom onset, or a CRP level of 4.0-10 mg / L at 21-36 months from symptom onset. CRP level of 4.2-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.3-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.3-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.4-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.5-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.6-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.7-6.0 mg / L for 21-36 months from symptom onset CRP level of 4.8-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4.9-6.0 mg / L for 21-36 months from symptom onset, CRP level of 4-10 mg / L for 21-30 months from symptom onset, CRP level of 5.1-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.2-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.3-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.4-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.5-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.6-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.7-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.8-6.0 mg / L for 21-36 months from symptom onset, CRP level of 5.9-6.0 mg / L for 21-30 ... A CRP level of 5.3-6.0 mg / L for 21-36 months from symptom onset, a CRP level of 5.4-6.0 mg / L for 21-36 months from symptom onset, a CRP level of 5.5-6.0 mg / L for 21-36 months from symptom onset, a CRP level of 5.6-6.0 mg / L for 21-36 months from symptom onset, a CRP level of 5.7-6.0 mg / L for 21-36 months from symptom onset, a CRP level of 5.8-6.0 mg / L for 21-36 months from symptom onset, or a CRP level of 5.9-6.0 mg / L for 21-36 months from symptom onset. In some methods, the subject is between 40 and 65 years of age.

[0140] In any of the methods described herein, treating includes reducing the symptoms of ALS in the subject, reducing the progression of ALS, increasing life expectancy, or a combination thereof. In any of the methods described herein, treating results in no disease progression in the subject after administration using the ALS Functional Rating Scale (ALSFRS-R). In some methods, treating can include assessing the subject's disease progression using the ALS Functional Rating Scale (ALSFRS-R), and halting disease progression can include a reduction of 3 points or less in the ALSFRS-R over a 6-month period. Treating can also include halting disease progression. Treating can also include a change in lung function measured by slow vital capacity readings or a longer time to tracheotomy compared to subjects not treated with chlorite. Treating can also include reducing blood inflammatory biomarker levels in the subject. Treating can also include reducing CRP levels in the subject.

[0141] In any of the methods described herein, treating includes stopping ALS disease progression, including stopping the decrease in the patient's lung capacity. Treating can include stopping the decrease in the patient's lung capacity, including, for example, 0.05% or less, 0.075% or less, 0.1% or less, 0.125% or less, 0.15% or less, 0.2% or less, 0.225% or less, 0.25% or less, 0.275% or less, 0.3% or less, 0.5% or less, 0.75% or less, 1% or less, 1.25% or less, 1.5% or less, 1.75% or less, 2% or less, 3% or less, 4% or less, 5% or less, 6% or less, 7% or less, 8% or less, 9% or less, 10% or less, 12.5% ​​or less, 15% or less, 17.5% or less, 20% or less, 22.5% or less, or 25% or less decrease over a period of 6 months.

[0142] In any of the methods described herein, the subject is diagnosed with or has been diagnosed with ALS.The subject can be diagnosed based on electromyogram (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy.In some methods, the subject is diagnosed with or has been diagnosed with ALS at least 12 months or more before administration of chlorite. In some cases, at least 12 months or more includes at least 12 months or more, at least 13 months or more, at least 14 months or more, at least 15 months or more, at least 16 months or more, at least 17 months or more, at least 18 months or more, at least 19 months or more, at least 20 months or more, at least 21 months or more, at least 22 months or more, at least 23 months or more, at least 24 months or more, at least 25 months or more, at least 26 months or more, at least 27 months or more, at least 28 months or more, at least 29 months or more, or at least 30 months or more.At least 12 months or longer may be as long as 30, 40, 50, or 60 months, e.g., the subject has been in the study for 12 months to 60 months, 12 months to 50 months, 12 months to 40 months, 12 months to 30 months, 13 months to 60 months, 13 months to 50 months, 13 months to 40 months, 13 months to 30 months, 14 months to 60 months, 14 months to 50 months, 14 months to 40 months. , 14 months to 30 months, 15 months to 60 months, 15 months to 50 months, 15 months to 40 months, 15 months to 30 months, 16 months to 60 months, 16 months to 50 months, 16 months to 40 months, 16 months to 30 months, 17 months to 60 months, 17 months to 50 months, 17 months to 40 months, 17 months to 30 months, 18 months to 60 months, 18 months to 50 months, 18 months to 40 months, 18 months to 30 months, 19 months to 60 months, 19 months to 50 months, 19 months to 40 months, 19 months to 30 months, 20 months to 60 months, 20 months to 50 months, 20 months to 40 months, 20 months to 30 months, 21 months to 60 months, 21 months to 50 months, 21 months to 40 months, 21 months to 30 months, 22 months to 60 months, 22 months to 50 months, 22 months diagnosed with ALS or been diagnosed with ALS for 22 months to 40 months, 22 months to 30 months, 23 months to 60 months, 23 months to 50 months, 23 months to 40 months, 23 months to 30 months, 24 months to 60 months, 24 months to 50 months, 24 months to 40 months, 24 months to 30 months, 25 months to 60 months, 25 months to 50 months, 25 months to 40 months, or 25 months to 30 months.

[0143] In some methods, chlorite comprises sodium chlorite.In some methods, treating the subject with chlorite can comprise intravenously administering chlorite or its pharma- ceutically acceptable salt (e.g., sodium chlorite) at a dose of 2mg / kg for 5 days every day for the first month, and then for 3 consecutive days every month thereafter for 6 months, for approximately 60 minutes, using an infusion pump.

[0144] In some methods, chlorite comprises sodium chlorite or a pharma- ceutically acceptable salt thereof. In some methods, treating the subject with chlorite may comprise administering chlorite or a pharma- ceutically acceptable salt thereof (e.g., sodium chlorite) intravenously for approximately 30 minutes using an infusion pump at a dose of 1 mg / kg, 2 mg / kg, or 3 mg / kg. Treatment may further comprise administering 20 infusions over 6 cycles for a period of 25 weeks. Cycle 1 may comprise daily infusions for 5 consecutive days (e.g., 5 infusions over a period of 1 week). Cycles 2, 3, 4, 5, and 6 may comprise daily infusions for 3 consecutive days (e.g., 3 infusions over a period of 1 week).

[0145] In some methods, the treatment may include administering chlorite or a pharma- ceutically acceptable salt thereof (e.g., sodium chlorite) intravenously as a 30-minute infusion at a dose of 1.6, 2.0, or 3.2 mg / kg (of chlorite). The treatment may further include administering approximately 90 such infusions approximately every other day over a period of six months.

[0146] In some methods, the treatment may include administering chlorite or a pharma- ceutically acceptable salt thereof (e.g., sodium chlorite) intravenously as a 30-minute or 60-minute infusion at a dose of 1.5, 2.0, 2.5, or 3.0 mg / kg (as chlorite).The treatment may further include administering approximately 90 such infusions approximately every other day over a period of 6 months, or 180 such infusions daily over a period of 6 months.

[0147] In some methods, the treatment may include administering a pharmaceutical composition containing chlorite or its pharma- ceutical acceptable salt (e.g., sodium chlorite) daily as a 30-minute infusion at a dose of 1.0, 1.5, 2.0, 2.5, or 3.0 mg / kg. The treatment may further include administering approximately 180 such daily infusions over a period of 6 months.

[0148] In some methods, the treatment may include administering to a young ALS patient a pharmaceutical composition comprising chlorite or its pharma- ceutical acceptable salt (e.g., sodium chlorite), e.g., sodium chlorite, intravenously for approximately 60 minutes using an infusion pump at a dose of 1 mg / kg, 2 mg / kg, or 3 mg / kg. The treatment may further include administering 20 infusions over 6 cycles for a period of 25 weeks. Cycle 1 may include daily infusions for 5 consecutive days (e.g., 5 infusions over a period of 1 week). Cycles 2, 3, 4, 5, and 6 may include daily infusions for 3 consecutive days (e.g., 3 infusions over a period of 1 week).

[0149] In some methods, the treatment may include administering to an endometriosis patient a pharmaceutical composition comprising chlorite or its pharma- ceutical acceptable salt (e.g., sodium chlorite), for example, sodium chlorite, intravenously for approximately 60 minutes using an infusion pump at a dose of 1 mg / kg, 2 mg / kg, or 3 mg / kg. The treatment may further include administering 20 infusions over 6 cycles for a period of 25 weeks. Cycle 1 may include daily infusions for 5 consecutive days (e.g., 5 infusions over a period of 1 week). Cycles 2, 3, 4, 5, and 6 may include daily infusions for 3 consecutive days (e.g., 3 infusions over a period of 1 week).

[0150] Treatment using the methods disclosed herein may also be accomplished using potassium chlorite, or a pharma- ceutically acceptable salt thereof.

[0151] In an exemplary embodiment, the method may be carried out as described in Examples 1-4 below. EXAMPLES

[0152] The following are examples of the methods of patient selection and treatment disclosed herein. The data presented in this disclosure are drawn from two 6-month Phase 2 studies conducted with NP001 in ALS patients, which are registered with ClinicalTrials.gov (NCT01281631 for Phase 2A and NCT02794857 for Phase 2B). NP001 Drug Product (DP) is a clear, colorless, sterile solution of sodium chlorite and contains no preservatives. NP001 DP contains purified sodium chlorite (5.61 mg / mL, 62 mM), disodium hydrogen phosphate (0.107 mg / mL), and sterile water for injection, at pH 7.5-9.5. The active moiety is chlorite, and all clinical doses are expressed as mg / kg of chlorite. Sodium chlorite (62 mM) at a concentration of 5.61 mg / mL converts to 4.2 mg / mL chlorite (62 mM). The formulation is packaged in 30 mL type 1 flint glass vials with 20 mM stoppers and capped with a red aluminum overseal. Each single-use 30 mL vial delivers 20 mL (nominal) of NP001. The formulation is not intended for IV administration undiluted. Dose preparation instructions specify that the formulation be combined with 0.45% sodium chloride (half normal saline obtained from a commercial supplier) prior to administration to obtain an exact total volume of 250 mL of infusion solution.

[0153] The data focuses on pre-study disease progression rate, baseline plasma C-reactive protein (CRP) levels, and clinical outcomes in subjects who received 2 mg / kg NP001 (a pharmaceutical composition comprising sodium chlorite) or placebo. Statistical analysis was performed using SAS 9.4 (SAS Institute, Cary, North Carolina, USA). For all analyses, a two-sided p-value of less than 0.05 was considered statistically significant. The patient selection method is based on statistical analysis of data from clinical trials and represents actual patients with the described characteristics who were actually treated with a pharmaceutical composition comprising sodium chlorite or placebo. However, the patient selection method and treatment method are not part of the clinical trial and are an embodiment of the present disclosure.

[0154] The Phase 2A trial enrolled 138 ALS patients within 3 years of symptom onset and had three equal arms; placebo, 1 mg / kg, and 2 mg / kg of NP001 (a pharmaceutical composition containing sodium chlorite).

[0155] The data showing NP001 sensitivity correspond to ALS patients with a slower progression, a longer time since ALS symptom onset, and the only subset with evidence of inflammation (high blood granulocyte percentage). The elevated CRP after 21 months may indicate the presence of an ongoing inflammatory process operating in this large subset of ALS disease.

[0156] The Phase 2B trial was conducted at 21 sites in the United States and one in Canada from August 2016 to December 2017. The study was fully enrolled and did not terminate prematurely. Participants were men and women with a diagnosis of probable or definite ALS according to the El Escorial criteria. Participants were required to have onset of ALS-related weakness within 3 years, an SVC greater than 65% predicted, and a clinical life expectancy greater than 6 months. All participants were required to have high-sensitivity CRP (hs-CRP) levels at screening of at least 1.13 mg / L or higher, the median value shown in the Phase 2A trial. Participants receiving riluzole had to have been on a stable dose for 30 days. Individuals using continuous positive airway pressure or bilevel positive airway pressure, those with active lung disease, and those receiving recent immunotherapy were excluded.

[0157] The study was randomized, double-blind, and placebo-controlled, and the study drug was administered over six cycles. Participants were assigned in a 1:1 manner to NP001 (a pharmaceutical composition containing sodium chlorite) 2 mg / kg / day (chlorite salt) or placebo, and stratified by ALS site of onset (bulbar / limb type). The study drug was infused over 30 minutes via an infusion pump. Participants received a total of 20 infusions over six monthly cycles, as previously defined. There was one month between the start of each cycle. Cycle 1 consisted of daily infusions for five consecutive days. Cycles 2, 3, 4, 5, and 6 consisted of daily infusions for three consecutive days, respectively. The randomized population that received at least one dose of a pharmaceutical composition containing sodium chlorite or placebo and had at least one post-baseline ALSFRS-R total score assessment was predefined as the modified intention to treat (mITT) population. Investigators, site personnel, and ALSFRS-R assessors remained blinded to treatment allocation throughout the study. An independent data monitoring committee assessed safety periodically during the trial.

[0158] All randomized participants who received at least one dose of study drug will be included in the analysis and summary of safety data. Tolerability and safety were assessed by adverse event (AE) reporting, vital signs, ECG, laboratory parameters, physical examination, and formal phlebitis scoring.

[0159] Participants were reviewed for efficacy and safety assessments at monthly intervals. The primary efficacy measure in this study was the change from baseline in mean ALSFRS-R score after 6 months of treatment. Secondary efficacy measures included the percentage change from baseline in mean predicted SVC after 6 months of treatment, and the percentage of participants who did not worsen (non-progressors) as assessed by the change from baseline in ALSFRS-R score after 6 months of treatment.

[0160] Statistical analysis was performed using SAS 9.4 and JMP Pro 16 (SAS Institute, Cary, North Carolina, USA). In general, data were summarized using counts and percentages for categorical data and standard univariate descriptive statistics (number of participants, mean, standard deviation, median) for continuous data. Percentages were compared between placebo and the pharmaceutical composition containing sodium chlorite for non-progressors using Fisher's exact test. For continuous data, placebo was compared with each of the pharmaceutical composition groups containing sodium chlorite using an analysis of covariates model. For all analyses, a two-sided p-value of less than 0.05 was considered statistically significant.

[0161] Duration of ALS at baseline was defined as the number of months from onset of ALS symptoms. Mean disease progression (DP) at baseline was assessed using the following formula:

number

[0162] Example 1 Treatment of a Subpopulation of ALS Patients with Chlorite (Phase 2A Results) Treatment of an ALS patient with NP001 (a pharmaceutical composition comprising sodium chlorite) begins with identifying the patient as a candidate for such treatment with a pharmaceutical composition comprising sodium chlorite based on patient characteristics that place the patient within a target ALS patient population that is likely to be responsive to treatment with a pharmaceutical composition comprising sodium chlorite. In this example, these characteristics include any patient with ALS.

[0163] A Phase 1 controlled trial of NP001 in patients with ALS demonstrated safety, tolerability, and dose-dependent downregulation of monocyte activation. A Phase 2A study evaluated the safety, tolerability, and preliminary efficacy of NP001 in slowing the progression of ALS. A small, non-significant trend toward slowing progression was observed, which was highest in patients with elevated systemic inflammation at baseline. Elevated inflammation was defined as having plasma wide-range C-reactive protein (wr-CRP) values ​​above 1.13 mg / L, in which the change from baseline in the ALSFRS-R scale was -2.2 points over the 6-month treatment period, compared with -5.1 points in the placebo group. In addition, more than twice as many patients (25%) did not progress during the 6-month treatment period in the high-dose pharmaceutical composition containing sodium chlorite, compared with placebo (11%). Most "non-progressors" had elevated baseline inflammatory biomarkers. Inflammation-associated IL-18 and lipopolysaccharide (LPS) levels, which were elevated at baseline, normalized after treatment with 2 mg / kg NP001.

[0164] Example 2 Treatment of a Subpopulation of ALS Patients with Chlorite (Phase 2B Results) Approximately 300 subjects were screened and randomized, 68 to placebo and 70 to NP001. 117 participants completed the planned dosing. Figure 1 shows a flow chart of individual treatment in the Phase 2B study. Note that one placebo and three NP001 patients discontinued the study after the start of the study to start treatment with edaravone, which is approved for the treatment of ALS. The only significant difference in TEAEs between NP001 and placebo was the higher rate of infusion-related side effects in the NP001 group. Infusion-related burning resolved for most patients by slowing the infusion rate.

[0165] Treatment of an ALS patient with NP001 (a pharmaceutical composition comprising sodium chlorite) begins with identifying the patient as a candidate for such treatment with a pharmaceutical composition comprising sodium chlorite based on patient characteristics that place the patient within a target ALS patient population likely to be responsive to treatment with a pharmaceutical composition comprising sodium chlorite. In this example, these characteristics include patients with elevated C-reactive protein (CRP) levels of at least 1.13 mg / L or greater, stable disease, and patients between the ages of 40 and 65.

[0166] In the active drug arm, patients will be treated with NP001 at a dosage of 2 mg / kg chlorite as a 60 minute drug infusion for 5 days in the first month, followed by 3 consecutive days per month for the following 5 months.

[0167] Patients are then assessed weekly for ALS disease progression using the ALS Functional Rating Scale (ALSFRS-R) and by measuring vital capacity (VC). ALSFRS-R assessment is performed using a questionnaire-based method. VC is measured using a spirometer.

[0168] One of the most common adverse events was pain at the injection site, which was found to be mitigated by slowing the infusion from 30 to 60 minutes.

[0169] The primary endpoint in each of the phase 2 studies was the change from baseline in ALSFRS-R scores in participants who received a pharmaceutical composition containing 2 mg / kg sodium chlorite or a placebo over the 6-month study. The secondary endpoint in each study was the percent change in predicted vital capacity (VC) over the 6-month study, which serves as a predictor of mortality in ALS patients. The phase 2A study assessed the percent change in predicted VC in forced vital capacity (FVC), while the phase 2B study assessed the percent change in predicted VC in SVC. The percent change in predicted VC from baseline values ​​between FVC and SVC was comparable, and therefore the evaluation of the effect of the pharmaceutical composition containing sodium chlorite on VC change combined from both studies was normalized to the "percent change in predicted VC from baseline [100 x (predicted VC at end of study - predicted VC at baseline) / predicted VC at baseline]". Plasma concentrations of wr-CRP were measured as an exploratory biomarker for phase 2A. For phase 2B, plasma hs-CRP values ​​were used as one of the entry criteria. To combine the two sets of CRP data from Phase 2A and Phase 2B for data analysis, plasma wr-CRP values ​​from Phase 2A were converted to hs-CRP using a simple calibration equation by Ziv-Baran et al. to correct wr-CRP values ​​(corrected wrCRP=0.3136+0.8803×wrCRP). Analysis of baseline disease clinical and demographic factors was performed by treatment group.

[0170] FIG. 2 shows the change from baseline in ALSFRS-R change scores for all patients in the study. The change from baseline in ALSFRS-R scores for participants treated with a pharmaceutical composition containing sodium chlorite is shown in blue (n=68) and compared to the placebo group (n=68) shown in red. Bars represent the mean ± SEM of the change from baseline in ALSFRS-R scores. By the end of the study, no difference was found between the pharmaceutical composition containing sodium chlorite group and the placebo group (pharmaceutical composition containing sodium chlorite=-4.3 vs. placebo=-4.3) (Wilcoxon test, p=0.71). FIG. 3 shows a graph of the change in vital capacity for subjects treated with a pharmaceutical composition containing sodium chlorite versus placebo. The mean percent change from baseline in predicted SVC for participants treated with a pharmaceutical composition containing sodium chlorite (n=68) is shown in blue and compared to the placebo group (n=68) shown in red. Bars represent the mean ± SEM of the percent change from baseline in predicted SVC. By the end of the study, there was no significant difference between patients treated with a pharmaceutical composition containing sodium chlorite and placebo (pharmaceutical composition containing sodium chlorite = -10.8% vs. placebo = -13.1%) (Wilcoxon test, p = 0.15). Figure 4 shows a bar graph of the progression-free rate of subjects treated with a pharmaceutical composition containing sodium chlorite versus placebo. The progression-free rate of non-progressors is defined as no decrease in ALSFRS-R score from baseline to 6 months. The proportion of non-progressors (progression-free rate) in the treatment with a pharmaceutical composition containing sodium chlorite at 2 mg / kg (13 of 55) was similar to the placebo group (12 of 62) (Fisher's exact test, p = 0.65). Figure 5 shows an age distribution chart of subjects who did not progress during the study. Age distribution plot showing increasing participant age (in years) on the X-axis and the number of participants in a particular age category on the Y-axis.The top panel represents the age distribution of non-progressors treated with a pharmaceutical composition comprising sodium chlorite; 13 of the non-progressors treated with a pharmaceutical composition comprising sodium chlorite in the Phase 2B group (all of the non-progressors in the pharmaceutical composition comprising sodium chlorite in Phase 2B) fell in the age range of 40-65 years (top panel, n=13), whereas only 5 of 12 placebo non-progressors were in the age range of 40-65 years (bottom panel, n=12) (Fisher's exact test, p=0.002).

[0171] Three efficacy outcome measures were defined at the start of the Phase 2B study and were reported at the end of the study. No significant differences were found. Changes from baseline showed similar rates of decline in both ALSFRS-R score and % change in predicted vital capacity for the pharmaceutical composition containing sodium chlorite and placebo (Figures 2 and 3). Analysis of % non-progressors among those who completed the study showed no differences between the pharmaceutical composition containing sodium chlorite and placebo groups.

[0172] When assessed solely on the basis of treatment with the pharmaceutical composition containing sodium chlorite, there is no clinically significant difference in reduction between the two groups.

[0173] Example 3 Treatment of a subpopulation of ALS patients with chlorite (post-hoc analysis) Treatment of an ALS patient with NP001 (a pharmaceutical composition comprising sodium chlorite) begins with identifying the patient as a candidate for such treatment with a pharmaceutical composition comprising sodium chlorite based on patient characteristics that place the patient within a target ALS patient population likely to be responsive to treatment with a pharmaceutical composition comprising sodium chlorite. In this example, these characteristics include patients with elevated C-reactive protein (CRP) levels of at least 1.13 mg / L or greater, stable disease, and patients between the ages of 40 and 65.

[0174] Patients will be treated with NP001 (a pharmaceutical composition containing sodium chlorite) at a dosage of 2 mg / kg of chlorite as a 60 minute drug infusion for 5 days in the first month, followed by 3 consecutive days per month for the following 5 months.

[0175] Patients are then assessed weekly for ALS disease progression using the ALS Functional Rating Scale (ALSFRS-R) and by measuring vital capacity (VC). ALSFRS-R assessment is performed using a questionnaire-based method. VC is measured using a spirometer.

[0176] It was observed that patients treated with the pharmaceutical composition comprising sodium chlorite described in this Example experienced a slowing of disease progression beginning at initiation as measured by assessment of change from baseline in ALSFRS-R; a slowing of respiratory function decline beginning at 1 month post-initiation in a time window that overlapped with the effect of ALSFRS-R on drug administration effect, supporting the overall conclusion of a slowing of disease progression in a significant proportion of ALS patients.

[0177] FIG. 6 shows a flow chart summarizing the subject distribution of combination participant allocation within the study, including classification of patients aged 40-65 years with plasma CRP levels above 1.13 mg / L treated with NP001 versus placebo. FIG. 7 shows a graph of the change from baseline in ALSFRS-R score versus placebo for patients aged 40-65 years with plasma CRP levels above 1.13 mg / mL treated with NP001. Change from baseline in ALSFRS-R score for participants treated with NP001 (n=56) is shown in blue and compared to the placebo group (n=61) shown in red. Bars represent the mean ± SEM of the change from baseline in ALSFRS-R score. The NP001-treated group showed a 36% slower progression rate by the end of the study (Wilcoxon test, p=0.01). FIG. 8 shows a graph of the percent change from baseline in vital capacity for patients aged 40-65 years with plasma CRP above 1.13 mg / mL treated with NP001 versus placebo. The percent change from baseline in predicted VC for participants treated with NP001 (n=56) is shown in blue and compared to the placebo group (n=61) shown in red. Bars represent the mean ± SEM of the % change from baseline in predicted VC. Mean % VC reduction over the 6-month study: NP001: -7.5% (-1.3% per month), placebo: -15.4% (-2.6% per month). The NP001 treatment arm had 51% less reduction in respiratory function than the placebo arm by the end of the study (Wilcoxon test, p<0.001). Figure 9 shows a bar graph of progression-free rates for subjects aged 40-65 years with plasma CRP above 1.13 mg / mL treated with NP001 (a pharmaceutical composition containing sodium chlorite) versus placebo. Non-progressors, defined as no decrease in ALSFRS-R score from baseline to 6 months by treatment group, were restricted to those with plasma CRP above 1.13 mg / L at baseline and age 40-65 years in Phase 2A and 2B studies. The proportion of non-progressors (progression-free rates) in the 2 mg / kg NP001 treatment group (19 of 56) was significantly higher than that in the placebo group (7 of 61) (Fisher's exact test, p=0.004).In participants with plasma CRP greater than 3 mg / L at baseline, the progression-free rate was 46% (13 / 28) when treated with a pharmaceutical composition containing sodium chlorite compared with 4.5% (1 / 22) in the placebo group (Fisher's exact test, p=0.001).

[0178] It was observed that patients aged 40-65 years with plasma CRP above 1.13 mg / mL who were treated with NP001, as opposed to placebo, experienced a slowing of ALS disease progression, which corresponded to reduced ALSFRS-R score decline, reduced lung capacity decline, and increased progression-free rates.

[0179] In Phase 2B, of the total 117 participants who completed the study, 13 participants in the NP001 group and 12 participants in the placebo group did not progress. Demographic analysis of these participants identified a nonrandom age association in NP001 nonprogressors compared with placebo nonprogressors (Fisher's exact test, p=0.002). NP001-treated nonprogressors were within the age range of 40-65 years. Placebo nonprogressors spanned the entire age range within the Phase 2B study (32-76 years). This nonrandom age association with NP001 treatment was confirmed by follow-up assessment of NP001 nonprogressors in the Phase 2A study, who were also within the age range of 40-65 years.

[0180] The 154 participants with baseline plasma hs-CRP above 1.13 mg / L had completed either Phase 2A or 2B. The following table shows the baseline demographics and characteristics of the 154 participants included in the post-hoc evaluation by treatment group. Based on the initial observation of non-progressor characteristics in Phase 2B, a subset of individuals aged 40-65 years from this combined cohort of 154 participants from both the pharmaceutical composition containing sodium chlorite treatment group and the placebo treatment group was selected for efficacy evaluation. The selection process for this final group is shown in Figure 6. Approximately 76% (117) of the 154 participants who completed the study fell into the 40-65 year old age group, all of whom had plasma CRP above 1.13 mg / L. The demographics of this smaller group were similar to the overall Phase 2 combined demographics. Baseline demographics and characteristics of participants in the Phase 2A and 2B studies were included in post-hoc assessments by treatment group. [Table 4-1] [Table 4-2] [1] Months from ALS symptom onset to baseline

[0181] Among 117 evaluable participants aged 40-65 years, the change in ALSFRS-R score and the % change in predicted VC score from baseline to the end of the study were calculated by treatment (Figures 7 and 8). Compared to the placebo group, the NP001 group showed a slower decline in ALSFRS-R score (36%, Figure 7) (p=0.01). In addition, patients treated with NP001 had a 51% slower slowing of VC decline compared to placebo (Figure 8) (p<0.001).

[0182] Participants who did not show a decrease in ALSFRS-R score over 6 months (non-progressors from both the treatment and placebo groups) were significantly more likely to have NP001 treatment (Figure 9). Over the same time frame, 34% (19 / 56) of participants treated with a pharmaceutical composition containing sodium chlorite were non-progressors compared to 11% (7 / 61) of placebo (p=0.004). Higher baseline CRP levels were observed in non-progressors treated with a pharmaceutical composition containing sodium chlorite compared to non-progressors in the placebo group. Among participants who had even higher CRP levels above 3 mg / L at baseline, 46% (13 / 28) of participants treated with a pharmaceutical composition containing sodium chlorite were non-progressors compared to 4.5% (1 / 22) of placebo (Fisher's exact test, p=0.001).

[0183] In ALS patients, the decline in respiratory vital capacity translates directly into poor survival. Similar to the variability seen in ALSFRS-R score comparisons, changes in respiratory function in ALS patients are reproducible over time, regardless of whether the measure is FVC or SVC. Natural history studies of VC over time in ALS patients confirm an average decline in respiratory function of 2.5-3% per month. In this post-hoc analysis, a pharmaceutical composition containing sodium chlorite slowed the decline in respiratory VC to 1.3% per month, compared to the placebo group, which had a decline of 2.6% per month.

[0184] Some results of the study are summarized in the table below: [Table 5]

[0185] Evaluation of NP001 activity showed that the percentage of non-progressors was significantly higher in the NP001 treatment arm than in the placebo arm over the 6-month study. In patients with clinically significant plasma CRP levels (at least 3 mg / L or higher), there was a 10:1 response advantage for those treated with NP001 compared to placebo controls. Unlike the activity of any other class of drugs tested in ALS patients, administration of NP001 (a pharmaceutical composition containing sodium chlorite) was associated with disease stabilization for at least 6 months in a significant subset of patients. Furthermore, consistent with the anti-inflammatory activity of the pharmaceutical composition containing sodium chlorite, patients who benefited from treatment were more likely to have higher inflammation levels as defined by blood CRP levels.

[0186] Patients who do not have any reduction in ALSFRS-R score are classified as having "stable" disease. Patients in both NP001-treated and placebo groups are scored for the proportion of patients with stable disease over the 6-month study. Pharmaceutical compositions containing sodium chlorite may stabilize symptom progression in a dose-dependent manner in a subset of patients.

[0187] In patients aged 40-65 years with plasma CRP of at least or above 1.13 mg / L, NP001 (a pharmaceutical composition containing sodium chlorite) treatment demonstrates a statistically significant reduction in decline in key physical function as measured by change in both ALSFRS-R and respiratory capacity scoring.

[0188] Example 4 Treatment of a Subpopulation of ALS Patients with Chlorite Treatment of an ALS patient with a pharmaceutical composition comprising sodium chlorite (e.g., NP001) begins with identifying the patient as a candidate for such treatment with a pharmaceutical composition comprising sodium chlorite based on patient characteristics that place the patient within a target ALS patient population likely to be responsive to treatment with a pharmaceutical composition comprising sodium chlorite. In this example, these characteristics include patients age 40-65 with stable disease who have elevated C-reactive protein (CRP) levels of at least 1.13 mg / L or greater, and the subject has sporadic ALS pathology.

[0189] In this example, sporadic ALS pathology includes cases where the subject does not have a family history of ALS (e.g., does not have inherited ALS pathology), where the subject does not have a mutation in an ALS-associated gene, and the subject has an ALS-associated gene mutation in any of the following genes: SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERB B4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD.

[0190] In the active drug arm, patients will be treated with a pharmaceutical composition containing sodium chlorite at a dosage of 2 mg / kg chlorite, administered as a 60-minute drug infusion for 5 days in the first month, followed by 3 consecutive days per month for the following 5 months.

[0191] Patients are then assessed weekly for ALS disease progression using the ALS Functional Rating Scale (ALSFRS-R) and by measuring vital capacity (VC). ALSFRS-R assessment is performed using a questionnaire-based method. VC is measured using a spirometer.

[0192] It is observed that the patients treated with the pharmaceutical composition comprising sodium chlorite described in this example experience a slowing of disease progression, measured by the evaluation of the change from baseline in ALSFRS-R, beginning at the onset time point; a slowing of respiratory function decline, beginning at 1 month after onset, in a time frame that overlaps with the effect of ALSFRS-R on drug administration effect, supporting the overall conclusion that a significant proportion of ALS patients experience a slowing of disease progression.It is further observed that an increased percentage of the patients treated with the pharmaceutical composition comprising sodium chlorite described in this example experience a slowing of disease progression, when compared with the cohort of Example 2, which does not constitute sporadic ALS pathology of subjects.

[0193] In patients aged 40-65 years with sporadic ALS pathology and plasma CRP of at least 1.13 mg / L or greater, treatment with a pharmaceutical composition containing sodium chlorite shows a statistically significant reduction in decline in key physical function as measured by change in both ALSFRS-R and respiratory capacity scoring.

[0194] Explanation of terms used in this disclosure The terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the disclosure. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, to the extent that the terms "including", "includes", "having", "has", "with" or variations thereof are used in either the detailed description and / or the claims, such terms are intended to be inclusive in a manner similar to the term "comprising".

[0195] The term "about" or "approximately" means within an acceptable range of error for a particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" may mean within 1 or more than 1 standard deviation, as is customary in the art. Alternatively, "about" may mean within a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term may mean within an order of magnitude, preferably within 5-fold, and more preferably within 2-fold, of a value. When a particular value is described in the present application and claims, the term "about" should be assumed to mean within an acceptable range of error for the particular value, unless otherwise indicated.

[0196] "Treatment," "treating," "alleviating," and "ameliorating" are used interchangeably as used herein. These terms refer to an approach to obtain a beneficial or desired outcome, including but not limited to therapeutic benefit and / or preventative benefit. Therapeutic benefit refers to eradication or amelioration of the underlying disorder being treated. Therapeutic benefit is also achieved by eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such that an improvement is observed in the patient, even though the patient may still be afflicted by the underlying disorder. For preventative benefit, the composition may be administered to a patient at risk of developing a particular disease or a patient reporting one or more of the physiological symptoms of the disease, but a diagnosis of the disease may not yet have been made.

[0197] The term "effective amount", "therapeutic amount" or "therapeutically effective amount" further described herein includes both this less effective amount and the normal effective amount, and indeed includes any amount that is effective to induce a particular condition, effect, and / or response. Therefore, the dose of any such co-administration subject may be less than that which may be used when administered alone. The effect of one or more of any such administration subject may be additive or synergistic. Any such administration subject may be administered more than once. The effective amount may vary depending on the intended application (in vitro or in vivo), or the subject and disease state being treated, such as the subject's weight and age, the severity of the disease state, the mode of administration, etc., which can be easily determined by those skilled in the art. The term also applies to a dose that will induce a particular response in target cells, such as reduced proliferation or downregulation of the activity of a target protein. The specific dose will vary depending on the particular compound selected, the dosing regimen followed, whether the compound is administered in combination with other compounds, the timing of administration, the tissue to which the compound is administered, and the physical delivery system by which the compound is delivered.

[0198] A "therapeutic effect" as used herein encompasses the therapeutic and / or prophylactic benefits described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0199] The term "pharmaceutically acceptable salts" refers to salts derived from various organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, etc. In some embodiments, the pharma-ceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0200] "Pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" includes any and all solvents, dispersion media, coating agents, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. The use of such media and agents for pharmaceutically active substances is well known in the art. Any conventional media or agent is contemplated for use in the therapeutic compositions of the present disclosure, except insofar as it is incompatible with the active ingredient. Supplementary active ingredients can also be incorporated into the composition.

[0201] "Subject" refers to an animal, e.g., a mammal, e.g., a human. The methods described herein can be useful in both preclinical human therapeutics and veterinary applications. In some embodiments, the subject is a mammal, and in some embodiments, the subject is a human.

[0202] The term "in vivo" refers to events that take place in the body of a subject.

[0203] Although embodiments of the present disclosure are shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided merely as examples. Those skilled in the art will recognize numerous variations, changes, and substitutions without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein can be used to implement the present disclosure. It is intended that the following claims define the scope of the present disclosure, as well as methods and structures within the scope of these claims, and their equivalents. Embodiment 1. A method for treating a subject with chlorite, wherein the subject has amyotrophic lateral sclerosis (ALS), the method comprising determining whether the subject is between 40 and 65 years of age, and administering the chlorite to the subject if the subject is between 40 and 65 years of age. 2. The method of embodiment 1, wherein the chlorite is not administered to the subject if the subject is not between 40 and 65 years old. 3. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject is between 45 and 65 years of age. 4. The method of any one of embodiments 1 to 3, wherein the subject has an elevated plasma C-reactive protein (CRP) level. 5. The method of embodiment 4, wherein said elevated plasma CRP level is greater than 3 mg / L of CRP in a plasma sample from said subject. 6. The method of any one of embodiments 1-3, further comprising the step of determining whether the subject has an elevated plasma C-reactive protein (CRP) level prior to administering the chlorite to the subject, and if the subject is between 40 and 65 years old and has an elevated plasma CRP level, then the chlorite is administered to the subject. 7. The method of embodiment 6, wherein the step of determining whether the subject has an elevated plasma CRP level comprises performing, or having an assay performed on, a plasma sample from the subject to determine the level of CRP in the plasma sample. 8. The method of embodiment 6 or embodiment 7, wherein said elevated plasma CRP level is greater than 3 mg / L of CRP in said plasma sample from said subject. 9. The method of embodiment 4 or embodiment 8, wherein the subject has an elevated plasma CRP level if the plasma sample has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 10. The method according to any one of embodiments 4 to 9, wherein the CRP level is or has been determined by latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or highly sensitive near-infrared particle immunoassay rate methods. 11. The method of any one of embodiments 1-10, wherein the subject has been experiencing symptoms of ALS for at least 12 months prior to administering the chlorite to the subject. 12. The method of any one of embodiments 1-10, further comprising the step of determining whether the subject has been experiencing symptoms of ALS for at least 12 months prior to administering the chlorite to the subject, wherein if the subject is between 40 and 65 years of age and has been experiencing symptoms of ALS for at least 12 months, then the chlorite is administered to the subject. 13. The method of embodiment 12, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS, or a combination thereof. 14. The method of any one of embodiments 11-13, wherein said symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 15. The method of any one of embodiments 11-14, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering the chlorite to the subject. 16. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising: (a) determining the subject's age and whether the subject has an elevated plasma C-reactive protein (CRP) level; and (b) administering chlorite to the subject if the subject is between 40 and 65 years old and has an elevated plasma CRP level. 17. The method of embodiment 16, wherein the chlorite is not administered to the subject if the subject is not between 40 and 65 years old. 18. The method of embodiment 16 or embodiment 17, wherein the chlorite is not administered to the subject if the subject does not have an elevated level of plasma CRP. 19. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject is between 40 and 65 years of age and has an elevated level of CRP. 20. The method of any one of embodiments 16-19, wherein a high level of plasma CRP is greater than 3 mg / L of CRP in a plasma sample from the subject. 21. The method of embodiment 20, wherein the high level of plasma CRP is greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L of CRP in the plasma sample from the subject. 22. The method according to any one of embodiments 16 to 21, wherein the CRP level is or has been determined by latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or highly sensitive near-infrared particle immunoassay rate methods. 23. The method of any one of embodiments 16-22, wherein the subject has been experiencing symptoms of ALS for at least 12 months prior to administering the chlorite to the subject. 24. The method of any one of embodiments 16-22, further comprising the step of determining whether the subject has been experiencing symptoms of ALS for at least 12 months prior to administering the chlorite to the subject, wherein if the subject is between 40 and 65 years of age, has an elevated level of plasma CRP, and has been experiencing symptoms of ALS for at least 12 months, the chlorite is administered to the subject. 25. The method of embodiment 24, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS, or a combination thereof. 26. The method of any one of embodiments 23-25, wherein said symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 27. The method of any one of embodiments 23-26, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering the chlorite to the subject. 28. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising: (a) determining the subject's age, whether the subject has an elevated level of plasma C-reactive protein (CRP), and whether the subject has been experiencing symptoms of ALS for at least 12 months; and (b) administering chlorite to the subject if the subject is between 40 and 65 years of age, has an elevated level of plasma CRP, and has been experiencing symptoms of ALS for at least 12 months. 29. The method of embodiment 28, wherein the chlorite is not administered to the subject if the subject is not between 40 and 65 years old. 30. The method of embodiment 28 or embodiment 29, wherein the chlorite is not administered to the subject if the subject does not have an elevated level of plasma CRP. 31. The method of any one of embodiments 28-30, wherein chlorite is not administered to the subject if the subject has not experienced symptoms of ALS for at least 12 months. 32. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject is between 40 and 65 years of age, has an elevated level of CRP, and has been experiencing symptoms of ALS for at least 12 months. 33. The method of any one of embodiments 28-32, wherein a high level of plasma CRP is greater than 3 mg / L of CRP in a plasma sample from said subject. 34. The method of embodiment 33, wherein the high level of plasma CRP is greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L of CRP in the plasma sample from the subject. 35. The method according to any one of embodiments 28 to 34, wherein the CRP level is or has been determined by latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or highly sensitive near-infrared particle immunoassay rate methods. 36. The method of any one of embodiments 28-35, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS, or a combination thereof. 37. The method of any one of embodiments 28-36, wherein said symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 38. The method of any one of embodiments 28-37, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering the chlorite to the subject. 39. A method for treating a subject with chlorite, wherein the subject has amyotrophic lateral sclerosis (ALS), the method comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has a CRP level greater than 3 mg / L, where if the plasma sample has a CRP level greater than 3 mg / L, then the subject has an elevated plasma CRP level; b) determining the length of time the subject has been experiencing symptoms of ALS; c) administering chlorite to the subject if the subject has an elevated plasma CRP level and has been experiencing symptoms of ALS for at least 12 months. A method comprising: 40. The method of embodiment 39, wherein the subject has an elevated plasma CRP level if the plasma sample has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 41. The method of embodiment 39 or embodiment 40, wherein the step of determining whether the plasma sample has a CRP greater than 3 mg / mL comprises latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or a highly sensitive near-infrared particle immunoassay rate method. 42. The method of any one of embodiments 39-41, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering chlorite to the subject. 43. The method of any one of embodiments 39-42, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS. 44. The method of any one of embodiments 39-43, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 45. The method of any one of embodiments 39-44, further comprising determining whether the patient is between 40 and 65 years of age, and administering chlorite to the subject if the patient is between 40 and 65 years of age. 46. ​​A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject: i) having elevated plasma C-reactive protein (CRP) levels as indicated by a plasma sample from said subject having CRP greater than 3 mg / L; ii) experiencing symptoms of ALS for at least 12 months prior to administration of said chlorite; method. 47. The method of embodiment 46, wherein the subject has an elevated plasma CRP level if the plasma sample has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 48. The method of embodiment 46 or embodiment 47, wherein the subject has been determined to have an elevated plasma CRP level by a method including latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or high-sensitivity near-infrared particle immunoassay rate methods. 49. The method of any one of embodiments 46-48, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering chlorite to the subject. 50. The method of any one of embodiments 46-49, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 51. A method for treating a subject with chlorite, the subject having amyotrophic lateral sclerosis (ALS), the method comprising: a) determining whether the subject has an elevated plasma C-reactive protein (CRP) level by performing or having performed an assay on a plasma sample from the subject to determine whether the plasma sample has a CRP level greater than 3 mg / L, where if the plasma sample has a CRP level greater than 3 mg / L, then the subject has an elevated plasma CRP level; b) administering chlorite to the subject if the subject has an elevated plasma CRP level. A method comprising: 52. The method of embodiment 51, wherein the subject has an elevated plasma CRP level if the plasma sample has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 53. The method of embodiment 51 or embodiment 52, wherein the step of determining whether the plasma sample has a CRP greater than 3 mg / mL comprises latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or a highly sensitive near-infrared particle immunoassay rate method. 54. The method of any one of embodiments 51-53, wherein prior to step (b), the subject has been experiencing symptoms of ALS for at least 12 months, at least 18 months, or at least 21 months. 55. The method of embodiment 54, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more of these. 56. The method of any one of embodiments 46 to 55, further comprising determining whether the patient is between 40 and 65 years of age, and administering chlorite to the subject if the patient is between 40 and 65 years of age. 57. A method for treating a subject with chlorite, the subject having amyotrophic lateral sclerosis (ALS), the method comprising: a) determining the length of time the subject has been experiencing symptoms of ALS; b) administering chlorite to the subject if the subject has been experiencing symptoms of ALS for at least 12 months. A method comprising: 58. The method of embodiment 57, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering chlorite to the subject. 59. The method of embodiment 57 or embodiment 58, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS. 60. The method of any one of embodiments 57-59, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 61. The method of any one of embodiments 57-60, wherein the sample of plasma from the subject has a CRP greater than 3 mg / L. 62. The method of embodiment 61, wherein a sample of plasma from the subject has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 63. The method of embodiment 61 or embodiment 62, wherein the CRP level in the sample of plasma from the subject is determined or has been determined by a method comprising latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or a highly sensitive near-infrared particle immunoassay rate method. 64. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject has elevated plasma CRP levels as indicated by a plasma sample from the subject having a CRP greater than 3 mg / L. 65. The method of embodiment 64, wherein the subject has an elevated plasma CRP level if the plasma sample has a CRP level greater than 3.9 mg / L. 66. The method of embodiment 64 or embodiment 65, wherein the subject has been determined to have an elevated plasma CRP level by a method including latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or high-sensitivity near-infrared particle immunoassay rate methods. 67. The method of any one of embodiments 64-66, wherein the subject has been experiencing symptoms of ALS for at least 12 months, at least 18 months, or at least 21 months prior to administration of the chlorite. 68. The method of embodiment 67, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more of these. 69. The method of any one of embodiments 57-68, further comprising determining whether the patient is between 40 and 65 years of age, and administering chlorite to the subject if the patient is between 40 and 65 years of age. 70. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising administering chlorite to the subject, wherein the subject has been experiencing symptoms of ALS for at least 12 months prior to administration of chlorite. 71. The method of embodiment 70, wherein the subject has been experiencing symptoms of ALS for at least 18 months or at least 21 months prior to administering chlorite to the subject. 72. The method of embodiment 70 or embodiment 71, wherein the step of determining the length of time the subject has been experiencing symptoms of ALS comprises reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS. 73. The method of any one of embodiments 70-72, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 74. The method of any one of embodiments 70-73, wherein the sample of plasma from the subject has a CRP greater than 3 mg / L. 75. The method of embodiment 74, wherein a sample of plasma from the subject has a CRP of greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 76. The method of embodiment 74 or embodiment 75, wherein the CRP level in the sample of plasma from the subject is determined or has been determined by a method comprising latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or a highly sensitive near-infrared particle immunoassay rate method. 77. The method of any one of embodiments 70-76, further comprising determining whether the patient is between 40 and 65 years of age, and administering chlorite to the subject if the patient is between 40 and 65 years of age. 78. The method of any one of embodiments 1-77, wherein treating comprises reducing symptoms of ALS, reducing progression of ALS, or increasing life expectancy in the subject, or a combination thereof. 79. The method of any one of embodiments 1 to 78, wherein treating comprises the absence of disease progression in the subject following administration using the ALS Functional Rating Scale (ALSFRS-R). 80. The method of any one of embodiments 1-79, wherein treating comprises a reduction in ALSFRS-R score of 3 points or less. 81. The method of any one of embodiments 1-80, wherein treating comprises a change in lung function as measured by slow vital capacity readings. 82. The method of any one of embodiments 1-81, wherein treating comprises a longer time to tracheotomy compared to a subject not treated with chlorite. 83. The method of any one of embodiments 1-82, wherein treating comprises reducing the level of a blood inflammatory biomarker. 84. The method of any one of embodiments 1-83, wherein the subject exhibits one or more symptoms of ALS based on electromyogram (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy, or a combination thereof. 85. The method of any one of embodiments 1-84, wherein the subject is diagnosed with or has been diagnosed with ALS. 86. The method of embodiment 85, wherein the subject has been diagnosed with ALS based on electromyogram (EMG), nerve conduction, magnetic resonance imaging (MRI), cerebrospinal fluid analysis, or muscle biopsy, or a combination thereof. 87. The method of embodiment 85 or embodiment 86, wherein the subject is or has been diagnosed with ALS at least 12 months prior to administration of the chlorite. 88. The method of any one of the preceding embodiments, wherein the chlorite comprises sodium chlorite. 89. The method of any one of the preceding embodiments, wherein the chlorite comprises potassium chlorite. 90. The method of any one of embodiments 1-89, wherein the chlorite is administered at 2 mg / kg body weight per dose. 91. The method of any one of embodiments 1-90, wherein the chlorite is administered intravenously. 92. The method of any of embodiments 1-91, wherein treating further comprises halting the decline in lung capacity in the subject. 93. The method of embodiment 92, wherein halting the decrease in the subject's vital capacity comprises a decrease in the subject's vital capacity of 0.05% or less, 0.075% or less, 0.1% or less, 0.125% or less, 0.15% or less, 0.2% or less, 0.225% or less, 0.25% or less, 0.275% or less, 0.3% or less, 0.5% or less, 0.75% or less, 1% or less, 1.25% or less, 1.5% or less, 1.75% or less, 2% or less, 3% or less, 4% or less, 5% or less, 6% or less, 7% or less, 8% or less, 9% or less, 10% or less, 12.5% ​​or less, 15% or less, 17.5% or less, 20% or less, 22.5% or less, or 25% or less over a 6 month period. 94. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising: determining that the subject has an elevated plasma C-reactive protein (CRP) level greater than 1.13 mg / L prior to administering NP001 chlorite; Prior to administering NP001 chlorite, determining that the subject is between 40 and 65 years old; administering NP001 chlorite intravenously over 60 minutes to the subject at a dose of 2 mg / kg body weight per dose for 5 days for one month; administering NP001 chlorite intravenously to the subject over a 60 minute period at 2 mg / kg body weight per dose for 3 consecutive days per month for the following 5 months; Including, the NP001 chlorite is at least 95% pure; The NP001 chlorite is pH balanced to a pH of 7.4. method. 95. The method of embodiment 1, further comprising the step of determining that the subject has an elevated plasma C-reactive protein (CRP) level greater than 3.00 mg / L. 96. Chlorite for use in treating amyotrophic lateral sclerosis (ALS) in a subject, wherein the subject has characteristics (i) to (iii): (i) the subject is between 45 and 65 years of age; and / or (ii) the subject has an elevated plasma level of CRP, and / or (iii) the subject has been experiencing symptoms of ALS for at least 12 months prior to the use of chlorite in their treatment; The chlorite salt has one or more of the following: 97. Chlorite for use according to embodiment 96, wherein characteristic (ii) is a plasma level of CRP greater than 1.13 mg / L. 98. Chlorite for use according to embodiment 96, wherein characteristic (ii) is a plasma level of CRP greater than 3 mg / L. 99. Chlorite for use according to embodiment 98, wherein characteristic (ii) is a plasma level of CRP greater than 3.1 mg / L, greater than 3.2 mg / L, greater than 3.3 mg / L, greater than 3.4 mg / L, greater than 3.5 mg / L, greater than 3.6 mg / L, greater than 3.7 mg / L, greater than 3.8 mg / L, greater than 3.9 mg / L, or greater than 4 mg / L. 100. Chlorite for use according to embodiments 96 to 99, wherein the subject has characteristics (i) and (ii). 101. Chlorite for use according to embodiments 96 to 100, wherein the subject has characteristics (i), (ii), and (iii). 102. Chlorite for use according to embodiments 96 to 101, wherein the subject has characteristics (ii) and (iii) and the elevated plasma level of CRP is greater than 1.13 mg / L. 103. Chlorite for use according to embodiments 96 to 102, wherein the subject has characteristics (ii) and (iii) and the elevated plasma level of CRP is greater than 3 mg / L. 104. Chlorite for use according to embodiments 96 to 103, in which the plasma level of CRP is or has been determined by latex agglutination, latex-enhanced nephelometry, photometric measurement of antigen-antibody reactions, or highly sensitive near-infrared particle immunoassay rate methods. 105. Chlorite for use according to embodiments 96 to 104, wherein in feature (iii) the length of time during which the subject has been experiencing symptoms of ALS is at least 18 months or at least 21 months prior to the use of chlorite in treating them. 106. Chlorite for use according to any one of embodiments 96 to 105, wherein the length of time that the subject has been experiencing symptoms of ALS is determined or has been determined by reviewing the subject's medical history for symptoms of ALS, reviewing the subject's medical history for a diagnosis of ALS, or querying the subject as to when they first began experiencing symptoms of ALS, or a combination thereof. 107. Chlorite for use according to embodiments 96 to 106, wherein the ALS symptoms in characteristic (iii) include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more thereof. 108. Treating (a) reduces the symptoms of ALS, reduces the progression of ALS, or increases life expectancy in the subject, or a combination thereof; (b) the subject has no disease progression after administration using the ALS Functional Rating Scale (ALSFRS R); (c) the subject has a 3 point or less decrease in ALSFRS R score; (d) the subject achieves a change in lung function as measured by slow vital capacity readings; (e) increases the time to tracheotomy compared to subjects not treated with chlorite; (f) reduces blood inflammatory biomarker levels; and / or (g) stops the subject's loss of vital capacity; and / or (h) the subject has a chlorite-treated inflammatory status of 0.05% or less, 0.075% or less, 0.1% or less, 0.125% or less, 0.15% or less, over a 6 month period. 108. The chlorite for use according to embodiments 96 to 107, wherein the chlorite achieves one or more of having a reduction in vital capacity of 0.2% or less, 0.225% or less, 0.25% or less, 0.275% or less, 0.3% or less, 0.5% or less, 0.75% or less, 1% or less, 1.25% or less, 1.5% or less, 1.75% or less, 2% or less, 3% or less, 4% or less, 5% or less, 6% or less, 7% or less, 8% or less, 9% or less, 10% or less, 12.5% ​​or less, 15% or less, 17.5% or less, 20% or less, 22.5% or less, or 25% or less. 109. Chlorite for use according to embodiments 96 to 108, wherein the subject exhibits one or more symptoms of ALS based on electromyogram, nerve conduction, magnetic resonance imaging, cerebrospinal fluid analysis, or muscle biopsy, or a combination thereof. 110. Chlorite for use according to embodiment 109, wherein the subject has been diagnosed with ALS based on electromyogram, nerve conduction, magnetic resonance imaging, cerebrospinal fluid analysis, or muscle biopsy, or a combination thereof. 111. Chlorite for use according to embodiments 96 to 110, wherein the subject is diagnosed with or has been diagnosed with ALS at least 12 months prior to the use of chlorite in their treatment. 112. The chlorite salt for use according to embodiments 96 to 111, comprising sodium chlorite or potassium chlorite. 113. Chlorite for use according to embodiments 96 to 112, administered at 2 mg / kg body weight per dose. 114. Chlorite for use according to embodiments 96 to 113, which is administered intravenously. 115. Chlorite for use according to embodiments 96 to 114, wherein the chlorite is administered intravenously to a subject over 60 minutes at 2 mg / kg body weight per dose for (a) 5 days for 1 month, then (b) 3 consecutive days per month for the following 5 months, wherein the chlorite is at least 95% pure and pH-balanced to a pH of 7.4. 116. Use of chlorite in the manufacture of a medicament for treating ALS, wherein the medicament is for use as defined in embodiments 96 to 115. 117. A sodium chlorite composition for use in treating amyotrophic lateral sclerosis (ALS) in a subject, wherein the sodium chlorite composition is administered intravenously to the subject over a 60 minute period, the sodium chlorite composition comprises purified sodium chlorite, the sodium chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight, the sodium chlorite composition is administered daily for 5 consecutive days in a first month and for 3 consecutive days in subsequent months, the purified sodium chlorite is at least 97% pure, the purified sodium chlorite comprises no more than 2.0% sodium chloride, the purified sodium chlorite comprises no more than 1.0% sodium chlorate, the sodium chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. 118. The sodium chlorite composition of embodiment 117, wherein (i) the progression of ALS in the subject is slowed, (ii) the decline in function in the subject is slowed, or (iii) the decline in lung capacity in the subject is slowed. 119. The sodium chlorite composition of embodiment 117, wherein the subject is 40 to 65 years old. 120. The sodium chlorite composition of embodiment 117, wherein the subject has a plasma C-reactive protein (CRP) level greater than 1.13 mg / L. 121. The sodium chlorite composition of embodiment 117, wherein the subject has a plasma hs-CPR level greater than 1.13 mg / L, or optionally, the subject has a plasma hs-CPR level greater than 3.0 mg / L. 122. The sodium chlorite composition of embodiment 117, wherein the subject has been experiencing symptoms of ALS for at least 18 months prior to the step of administering the sodium chlorite composition to the subject, and optionally the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more of these. 123. The sodium chlorite composition of embodiment 117, wherein the subject has sporadic ALS pathology. 124. The sodium chlorite composition of embodiment 117, wherein the subject does not have inherited ALS pathology. 125. The subject does not have a mutation in an ALS-associated gene, and optionally, the subject is selected from the group consisting of SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9o The sodium chlorite composition of embodiment 124, wherein the sodium chlorite composition does not have a mutation in rf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD. 126. A sodium chlorite composition for use in treating amyotrophic lateral sclerosis (ALS) in a subject having a plasma C-reactive protein (CRP) level greater than 1.13 mg / L, wherein the sodium chlorite composition is administered intravenously to the subject over a 60 minute period, the sodium chlorite composition comprises purified sodium chlorite, the sodium chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight, the sodium chlorite composition is administered daily for five consecutive days in a first month and three consecutive days in subsequent months, the purified sodium chlorite is at least 97% pure, the purified sodium chlorite comprises no more than 2.0% sodium chloride, the purified sodium chlorite comprises no more than 1.0% sodium chlorate, the sodium chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. 127. A sodium chlorite composition for use in treating amyotrophic lateral sclerosis (ALS) in a subject having a plasma hs-CRP level greater than 1.13 mg / L, wherein the sodium chlorite composition is administered intravenously to the subject over a 60 minute period, the sodium chlorite composition comprises purified sodium chlorite, the sodium chlorite composition is administered at 2 mg chlorite per kg of the subject's body weight, the sodium chlorite composition is administered daily for five consecutive days in a first month and three consecutive days in subsequent months, the purified sodium chlorite is at least 97% pure, the purified sodium chlorite comprises no more than 2.0% sodium chloride, the purified sodium chlorite comprises no more than 1.0% sodium chlorate, the sodium chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. 128. The sodium chlorite composition of any one of embodiments 126 or 127, wherein the subject is 40 to 65 years old. 129. A sodium chlorite composition for use in treating amyotrophic lateral sclerosis (ALS) in a subject between 40 and 65 years of age, wherein the sodium chlorite composition is administered intravenously to the subject over a period of 60 minutes, the sodium chlorite composition comprises purified sodium chlorite, the sodium chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight, the sodium chlorite composition is administered daily for 5 consecutive days in a first month and for 3 consecutive days in subsequent months, the purified sodium chlorite is at least 97% pure, the purified sodium chlorite comprises no more than 2.0% sodium chloride, the purified sodium chlorite comprises no more than 1.0% sodium chlorate, the sodium chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. 130. The sodium chlorite composition of embodiment 129, wherein the subject has a plasma hs-CRP level greater than 1.13 mg / L. 131. A sodium chlorite composition for use in treating amyotrophic lateral sclerosis (ALS) in a subject, wherein the sodium chlorite composition is administered intravenously to the subject over a 60 minute period, the sodium chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight, the sodium chlorite composition is administered daily for 5 consecutive days in a first month and 3 consecutive days in subsequent months, the purified sodium chlorite is at least 97% pure, the purified sodium chlorite contains 2.0% or less sodium chloride, the purified sodium chlorite contains 1.0% or less sodium chlorate, the sodium chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5, and the subject is (a) Age is between 40 and 65 years old; (b) plasma hs-CRP level greater than 1.13 mg / L; (c) experiencing symptoms of ALS for at least 18 months prior to administration of the sodium chlorite composition; (d) not having inherited ALS pathology; (e) not having a mutation in an ALS-related gene; and (f) not having a mutation in SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD; 1. A sodium chlorite composition having at least one ALS response factor selected from: 132. A method for treating amyotrophic lateral sclerosis (ALS) in a subject aged 40 to 65 years, comprising: administering intravenously to the subject a chlorite composition comprising purified sodium chlorite. Including, the chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight; The chlorite composition is administered daily for five consecutive days in a first month and daily for three consecutive days in subsequent months; The purified sodium chlorite is at least 97% pure; Purified sodium chlorite contains 2.0% or less sodium chloride, The purified sodium chlorite contains 1.0% or less sodium chlorate, The chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. method. 133. The method of embodiment 132, wherein the progression of ALS in the subject is slowed. 134. The method of any one of embodiments 132 to 133, wherein the decline in the subject's function is slowed. 135. The method of any one of embodiments 132 to 134, wherein the decrease in the subject's lung capacity is slowed. 136. The method of any one of embodiments 132 to 135, wherein the chlorite composition is administered over a period of 60 minutes. 137. The method of any one of embodiments 132 to 136, wherein the subject has a plasma C-reactive protein (CRP) level greater than 1.13 mg / L. 138. The method of any one of embodiments 132 to 137, wherein the subject has a plasma hs-CPR level greater than 1.13 mg / L. 139. The method of any one of embodiments 132 to 138, wherein the subject has a plasma hs-CPR level greater than 3.0 mg / L. 140. The method of any one of embodiments 132 to 139, wherein the subject has been experiencing symptoms of ALS for at least 18 months prior to the step of administering the chlorite composition to the subject. 141. The method of embodiment 140, wherein the symptoms of ALS include muscle weakness, muscle spasms, muscle cramps, muscle spasms, difficulty maintaining body position, difficulty chewing, slow or slurred speech, difficulty swallowing, increased salivation, decreased fine motor skills, difficulty climbing stairs, difficulty breathing, shortness of breath, decreased coordination, pain, fatigue, difficulty walking, increased clumsiness of movements, or a combination of two or more of these. 142. The method of any one of embodiments 132 to 141, wherein the subject has sporadic ALS pathology. 143. The method of any one of embodiments 132 to 142, wherein the subject does not have an inherited ALS pathology. 144. The method of any one of embodiments 132 to 143, wherein the subject does not have a mutation in an ALS-associated gene. 145. The subject is SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQS The method of any one of embodiments 132 to 144, wherein the patient does not have a mutation in TM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD. 146.1.1 A method of treating amyotrophic lateral sclerosis (ALS) in a subject with a plasma C-reactive protein (CRP) level greater than 3 mg / L, comprising: administering to the subject intravenously a chlorite composition comprising purified sodium chlorite. Including, the chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight; The chlorite composition is administered for five consecutive days in a first month and for three consecutive days in subsequent months; the purified sodium chlorite is at least 97% pure; the purified sodium chlorite contains 2.0% or less sodium chloride; the purified sodium chlorite contains 1.0% or less sodium chlorate; The chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. method. 147.1.1 A method of treating amyotrophic lateral sclerosis (ALS) in a subject with a plasma hs-CRP level greater than 3 mg / L, comprising: administering to the subject intravenously a chlorite composition comprising purified sodium chlorite. Including, the chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight; The chlorite composition is administered for five consecutive days in a first month and for three consecutive days in subsequent months; the purified sodium chlorite is at least 97% pure; the purified sodium chlorite contains 2.0% or less sodium chloride; The purified sodium chlorite contains 1.0% or less sodium chlorate. method. 148. The method of any one of embodiments 146-147, wherein the subject is 40 to 65 years old. 149. The method of any one of embodiments 146-148, wherein the chlorite composition is administered over a period of 60 minutes. 150. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising: administering to the subject intravenously over a period of 60 minutes a chlorite composition comprising purified sodium chlorite. Including, the chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight; The chlorite composition is administered for five consecutive days in a first month and for three consecutive days in subsequent months; the purified sodium chlorite is at least 97% pure; the purified sodium chlorite contains 2.0% or less sodium chloride; the purified sodium chlorite contains 1.0% or less sodium chlorate; The chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5. method. 151. The method of embodiment 150, wherein the subject has a plasma hs-CRP level greater than 1.13 mg / L. 152. The method of any one of embodiments 150-151, wherein the subject is 40 to 65 years old. 153. A method of treating amyotrophic lateral sclerosis (ALS) in a subject, comprising: administering to the subject intravenously a chlorite composition comprising purified sodium chlorite. Including, the chlorite composition is administered at 2 mg of chlorite per kg of the subject's body weight; The chlorite composition is administered daily for five consecutive days in a first month and daily for three consecutive days in subsequent months; the purified sodium chlorite is at least 97% pure; the purified sodium chlorite contains 2.0% or less sodium chloride; the purified sodium chlorite contains 1.0% or less sodium chlorate; the chlorite composition comprises disodium hydrogen phosphate and has a pH of 7.5 to 9.5; The object is (a) Age is between 40 and 65 years old; (b) plasma hs-CRP level greater than 1.13 mg / L; (c) experiencing symptoms of ALS for at least 18 months prior to administration of the chlorite composition; (d) not having inherited ALS pathology; (e) not having a mutation in an ALS-related gene; and (f) not having a mutation in SOD1, ALS2, chromosome 18, SEXT, SPG11, FUS, chromosome 20, VAPB, ANG, TARDBP / TDP-43, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, MATR3, TUBA4A, ANXA11, NEK1, C9orf72, CHCHD10, SQSTM1, TARDBP, SETX, TAF15, EWSR1, hnRNPA2B1, ELP3, TBK1, DCTN1, NEFH, PRPH, C19ORF12, SS18L1, PNPLA6, PON1-3, DAO, CHRNA3,4,B4, ALS3, ALS7, ALS6-21, or ALS-FTD; having at least one ALS response factor selected from method.

Claims

1. A composition for use in the treatment of amyotrophic lateral sclerosis (ALS), comprising sodium chlorite, said use comprising: a) contacting an aqueous pharmaceutical formulation of sodium chlorite with saline to provide a diluted sodium chlorite formulation, wherein the saline is a 0.45% sodium chloride solution and the diluted sodium chlorite formulation has a volume of 250 mL; and b) administering the diluted sodium chlorite formulation to a subject, wherein the subject has ALS and the subject has a plasma level of C-reactive protein greater than 1.13 mg / L. A composition for use comprising:

2. A composition for use as described in claim 1, wherein said administering is by injection.

3. The administering is by injection at an injection site, the injection is initiated as a 30-minute infusion, and the use comprises: c) determining that the subject experiences pain at the injection site during the injection; and d) slowing the infusion from 30 minutes to 60 minutes based on said determining that said subject experiences pain at the injection site.

2. The composition for use according to claim 1, further comprising:

4. A composition for use according to any one of claims 1 to 3, wherein the ALS is familial.

5. A composition for use according to any one of claims 1 to 3, wherein the ALS is sporadic.

6. A composition for use according to any one of claims 1 to 3, wherein the diluted sodium chlorite preparation is at a dosage of 2 mg per kg of the subject's body weight.

7. A composition for use according to any one of claims 1 to 3, wherein the aqueous pharmaceutical formulation of sodium chlorite has a sodium chlorite concentration of 62 mM.

8. A composition for use according to any one of claims 1 to 3, wherein the aqueous pharmaceutical formulation of sodium chlorite comprises sodium phosphate.

9. A composition for use according to any one of claims 1 to 3, wherein the aqueous pharmaceutical formulation of sodium chlorite has a pH of 7.5 to 9.

5.

10. A composition for use according to any one of claims 1 to 3, wherein the plasma level of C-reactive protein is determined by latex agglutination.

11. A composition for use according to any one of claims 1 to 3, wherein the plasma level of C-reactive protein is determined by latex-enhanced nephelometry.

12. A composition for use according to any one of claims 1 to 3, wherein the plasma level of C-reactive protein is determined by photometric measurement of the antigen-antibody reaction.

13. A composition for use according to any one of claims 1 to 3, wherein the plasma level of C-reactive protein is determined by a highly sensitive near-infrared particle immunoassay method.

14. A composition for use in the treatment of amyotrophic lateral sclerosis (ALS), comprising sodium chlorite, said use comprising: a) contacting an aqueous pharmaceutical formulation of sodium chlorite with saline to provide a diluted sodium chlorite formulation, wherein the saline is a 0.45% sodium chloride solution and the diluted sodium chlorite formulation has a volume of 250 mL; b) determining that the subject has ALS; c) determining that the subject has a plasma level of C-reactive protein greater than 1.13 mg / L; and d) administering the diluted sodium chlorite formulation to a subject based on the plasma level of C-reactive protein. A composition for use comprising:

15. The composition for use according to claim 14, wherein said administering is by injection.

16. The administering is by injection at an injection site, the injection is initiated as a 30-minute infusion, and the using comprises: c) determining that the subject experiences pain at the injection site during the injection; and d) slowing the infusion to 30 to 60 minutes based on said determining that said subject experiences pain at the injection site.

15. The composition for use according to claim 14, further comprising:

17. A composition for use according to any one of claims 14 to 16, wherein the ALS is familial.

18. A composition for use according to any one of claims 14 to 16, wherein the ALS is solitary.

19. A composition for use according to any one of claims 14 to 16, wherein the diluted sodium chlorite preparation is at a dosage of 2 mg per kg of the subject's body weight.

20. A composition for use according to any one of claims 14 to 16, wherein the aqueous pharmaceutical formulation of sodium chlorite has a sodium chlorite concentration of 62 mM.

21. A composition for use according to any one of claims 14 to 16, wherein the aqueous pharmaceutical formulation of sodium chlorite comprises sodium phosphate.

22. A composition for use according to any one of claims 14 to 16, wherein the aqueous pharmaceutical formulation of sodium chlorite has a pH of 7.5 to 9.

5.

23. A composition for use according to any of claims 14 to 16, wherein determining that the subject has a plasma level of C-reactive protein greater than 1.13 mg / L is by latex agglutination.

24. A composition for use according to any of claims 14 to 16, wherein determining that the subject has a plasma level of C-reactive protein greater than 1.13 mg / L is by latex-enhanced nephelometry.

25. A composition for use according to any one of claims 14 to 16, wherein determining that the subject has a plasma level of C-reactive protein greater than 1.13 mg / L is by photometric measurement of antigen-antibody reaction.

26. A composition for use according to any of claims 14 to 16, wherein determining that the subject has a plasma level of C-reactive protein greater than 1.13 mg / L is performed by a highly sensitive near-infrared particle immunoassay method.

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