Compositions and methods for treating Charcot-Marie-Tooth disease

Abstract

Disclosed herein is a method for treating Charcot-Marie-Tooth disease (CMTD) involving administering (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid or a pharmaceutical composition thereof to a patient suffering from symptoms of CMTD. Also disclosed are pharmaceutical compositions and kits of parts containing (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

Description

[Technical Field]

[0001] The present disclosure relates to (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid for use in the treatment of Charcot-Marie-Tooth disease (CMTD), pharmaceutical compositions thereof for use in the treatment of CMTD, and methods of treatment thereof. [Background technology]

[0002] Charcot-Marie-Tooth disease (CMTD), also known as hereditary motor and sensory neuropathy, is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of skeletal muscle tissue and function, as well as touch sensation throughout various parts of the body. This disease is the most common inherited neurological disorder affecting peripheral nerves, affecting approximately 1 in 2,500 people (Krajewski et al., 2000). CMTD is a heterogeneous disorder with over 100 different genes causally linked to CMT. It can be classified into four major disease types (Fridman et al., 2015): CMT1, CMT2, CMT4, and CMTX (Table 1).

[0003] [Table 1]

[0004] Progressive skeletal muscle weakness is a hallmark of CMT, with distal muscles (feet, hands, and lower legs) usually being more severely affected (Saporta et al., 2011). Most patients have the "classic" CMT phenotype, characterized by onset in the first two decades of life, distal muscle weakness, sensory loss, foot deformities (pes cavus and hammertoe), loss of grip strength, and absent Achilles tendon reflexes (Saporta et al., 2011). Quality of life (QoL) can be severely affected in patients with CMT, and impaired QoL is closely associated with symptoms of weakness and fatigue and loss of physical ability (Boentert et al., 2010; Vinci et al., 2005).

[0005] There are no approved treatments for CMT, therefore there is a need for treatments that can address muscle weakness, loss of grip strength, and generally improve the quality of life of CMT patients.

[0006] Skeletal muscle-specific ClC-1 chloride ion channels conduct inhibitory currents that oppose neuromuscular transmission. Inhibition of ClC-1 reduces the inhibitory current, thereby increasing muscle membrane excitability and improving neuromuscular transmission. This has been shown to result in recovery of muscle function under conditions that mimic neuromuscular disorders (Pedersen et al., 2021).

[0007] (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid (hereafter NMD670) is an inhibitor of the skeletal muscle-specific ClC-1 channel. The chemical structure of NMD670 is provided below.

[0008] [ka] (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid (NMD670)

[0009] NMD670 modifies the voltage sensitivity of ClC-1 channels, resulting in increased Cl in muscle fibers. - Inhibition of ClC-1 with NMD670 restores muscle activation under conditions of impaired neuromuscular transmission or impaired muscle fiber excitability, and under these conditions, NMD670 can restore force generation in skeletal muscle.

[0010] Therefore, ClC-1 channel has emerged as a target for potential drugs, but its potential has not been realized to a large extent.US Patent No. 10,385,028 discloses the synthesis of compounds designed to inhibit the action of ClC-1 channel to treat neuromuscular disorders.One of the compounds discussed in US Patent No. 10,385,028 is NMD670.

[0011] U.S. Patent No. 10,385,028 discloses a series of compounds capable of inhibiting ClC-1 channels to treat neuromuscular disorders, but does not discuss how these compounds could be used to design treatments that could effectively alleviate the broad range of symptoms associated with Charcot-Marie-Tooth disease. WO2020 / 254554 (incorporated herein by reference) discloses methods for producing NMD670.

[0012] Therefore, there is a need for safe and effective therapies to improve muscle function in patients with CMT. Summary of the Invention

[0013] The present disclosure relates to a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, the composition being for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid. The disclosure also relates to a kit-of-parts comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and a peripheral myelin protein 22 (PMP22) downregulator. [Brief explanation of the drawings]

[0014] [Figure 1]Figure 1 shows the first 30 end-plate potential (EPP) amplitude recordings from a single muscle fiber from a mouse soleus muscle. Intracellular recordings of EPPs were obtained from a single conotoxin-treated muscle fiber during 1-second motor nerve stimulation at 80 Hz in neuromuscular preparations isolated from wild-type (WT) (34 fibers) and CMT2D mice (60 fibers). Only fibers that were able to sustain EPP generation for the stimulation train were included in the above analysis. Mean EPP amplitudes with SEM are shown in Figure 1 for WT mice (black circles), CMT2D mice before treatment (open triangles), and CMT2D mice after treatment with NMD670 (gray squares). Although the mean EPP amplitude in CMT2D mice was lower than that in WT mice, a significant increase in EPP amplitude was observed after the addition of 10 μM NMD670 to CMT2D fibers in a paired t-test (p < 0.001). [Figure 2A] Action potentials were recorded from mouse soleus muscle fibers using intracellular electrodes during repeated stimulation of the motor nerve in an isolated neuromuscular preparation. Figure 2 shows action potential dysregulation during repeated stimulation of the motor nerve at different frequencies. To determine this, the number of action potentials not generated by nerve stimulation was determined for each fiber for each number of stimulation pulses in the stimulation train. Observations from all fibers were combined to obtain the percentage of action potential dysregulation across all fibers per group, which was plotted against the number of stimulations in the nerve stimulation pulse train. This was performed for two groups of fibers: before (black triangles) and after (gray squares) the addition of 10 μM NMD670. The average dysregulation rates were 3.6, 4.9, and 29.6% before, and 1.9, 0.8, and 20.4% after, the addition of NMD670 at 12 Hz (Figure 2A), 30 Hz (Figure 2B), and 80 Hz (Figure 2C), respectively. [Figure 2B]Action potentials were recorded from mouse soleus muscle fibers using intracellular electrodes during repeated stimulation of the motor nerve in an isolated neuromuscular preparation. Figure 2 shows action potential dysregulation during repeated stimulation of the motor nerve at different frequencies. To determine this, the number of action potentials not generated by nerve stimulation was determined for each fiber for each number of stimulation pulses in the stimulation train. Observations from all fibers were combined to obtain the percentage of action potential dysregulation across all fibers per group, which was plotted against the number of stimulations in the nerve stimulation pulse train. This was performed for two groups of fibers: before (black triangles) and after (gray squares) the addition of 10 μM NMD670. The average dysregulation rates were 3.6, 4.9, and 29.6% before, and 1.9, 0.8, and 20.4% after, the addition of NMD670 at 12 Hz (Figure 2A), 30 Hz (Figure 2B), and 80 Hz (Figure 2C), respectively. [Figure 2C] Action potentials were recorded from mouse soleus muscle fibers using intracellular electrodes during repeated stimulation of the motor nerve in an isolated neuromuscular preparation. Figure 2 shows action potential dysregulation during repeated stimulation of the motor nerve at different frequencies. To determine this, the number of action potentials not generated by nerve stimulation was determined for each fiber for each number of stimulation pulses in the stimulation train. Observations from all fibers were combined to obtain the percentage of action potential dysregulation across all fibers per group, which was plotted against the number of stimulations in the nerve stimulation pulse train. This was performed for two groups of fibers: before (black triangles) and after (gray squares) the addition of 10 μM NMD670. The average dysregulation rates were 3.6, 4.9, and 29.6% before, and 1.9, 0.8, and 20.4% after, the addition of NMD670 at 12 Hz (Figure 2A), 30 Hz (Figure 2B), and 80 Hz (Figure 2C), respectively. [Figure 3]This figure shows force and compound muscle action potential (CMAP) signals from the triceps surae muscle in the hind limb of a GarsP278KY mouse, a CMT2 mouse model. The animal was anesthetized and mechanically ventilated. The Achilles tendon was transected and attached to a force transducer with a string. The sciatic nerve was stimulated with an electrode inserted near the nerve. A separate electrode was used to record the CMAP electromyographic signal. This setup allowed for combined recording of CMAP and force from live animals. A) The left trace in the upper panel shows the force trace resulting from 10 pulses of 12 Hz stimulation in a representative mouse, showing a decrease in force with successive stimulations, indicated by the dotted line from the first peak. The left trace in the lower panel shows the CMAP recorded simultaneously from the same mouse during the same stimulation, also showing reduced amplitude with successive stimulations. After intravenous administration of 8 mg / kg NMD670, both the force and CMAP signals show less amplitude decrease with successive stimulations. B) The upper left panel shows force traces from a 1-second 120 Hz stimulus for a CMT animal in black, showing an initial peak in force production followed by a decrease in force for the remainder of the stimulus duration; in gray, force traces from a healthy mouse of similar age / sex from the same strain. The lower left panel shows CMAPs recorded simultaneously with the force traces. Force and CMAP improved after intravenous administration of 8 mg / kg NMD670 to CMT mice (right trace). C) shows the average improvement in force for 12, 30, and 120 Hz stimulation after intravenous administration of 8 mg / kg NMD670 in an experiment performed as described above. D) shows the relative CMAP amplitude of the fifth peak compared to the first peak during 120 Hz stimulation before and after intravenous administration of 8 mg / kg NMD670. [Figure 4] This shows the study design for a clinical observational study that enrolled patients with CMT types 1 and 2 and healthy age-matched controls at two research centers. Clinical tests are listed in order of testing. CMTES2: CMT test score 2. RNS: Repetitive nerve stimulation. SFEMG: Single-fiber EMG. *Only CMTES2 was performed at Visit 1. [Figure 5]Figure 1 shows jitter and blocking from Visit 1 of a clinical observational study of healthy subjects and CMT patients shown as individual data with medians for healthy controls and CMT patients (A and B) and for CMT1 and CMT2 patients (C and D). Mean consecutive difference (MCD). [Figure 6] Figure 1 shows the study design for the mouse CMT1A study. Abbreviations: CMAP, compound muscle action potential; [Figure 7] At each stimulation frequency, the difference in reduction for each individual animal with mean±SEM is shown. Circles=NMD670; triangles=vehicle, n=8 in both groups. [Figure 8] The difference in maximum stimulation torque for each individual animal with mean±SEM at each stimulation frequency is shown. Circles=NMD670; triangles=vehicle, n=8 in both groups. [Figure 9] Fade differences for each individual animal with mean±SEM at each stimulation frequency are shown. Circles=NMD670; triangles=vehicle, n=8 in both groups. [Figure 10] The study design is presented for a randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of NMD670 over 21 days in ambulatory adult patients with type 1 and type 2 Charcot-Marie-Tooth disease. [Figure 11A]Shows the schedule of activities during the clinical trial. Note: When possible, assessments should be conducted simultaneously at different visits. When possible, efficacy assessments should be conducted in the order listed in the SoA. Unscheduled visits may be conducted at any time. At unscheduled visits, all tests are optional and, if completed, should be reported on the CRF. Screening procedures may be conducted over several days within the 28-day screening period. The eligibility check conducted at the baseline visit involves checking that all eligibility criteria during the screening period have been met for randomization. Blood samples will be collected to test glucose concentrations after at least 4 hours of fasting as part of the safety laboratory evaluation. Abbreviations: 6MWT = 6-minute walk test; AE = adverse event; Cmax = maximum concentration; CMT-FOM = Charcot-Marie-Tooth Functional Outcome Measure; CMT-HI = Charcot-Marie-Tooth Health Index; CRF = case report form; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; EOT = end of treatment; FU = follow-up; HIV = human immunodeficiency virus; IMP = investigational medicinal product; IRT = interaction response technique; ONLS = global neuropathy limitation scale; PK = pharmacokinetics; SAE = serious adverse event; SF-36 = short form-36; sfEMG = single-fiber electromyography; SoA = schedule of activities; TUG = timed up-and-go test; V = visit; WOCBP = women of childbearing potential. [Figure 11B]Shows the schedule of activities during the clinical trial. Note: When possible, assessments should be conducted simultaneously at different visits. When possible, efficacy assessments should be conducted in the order listed in the SoA. Unscheduled visits may be conducted at any time. At unscheduled visits, all tests are optional and, if completed, should be reported on the CRF. Screening procedures may be conducted over several days within the 28-day screening period. The eligibility check conducted at the baseline visit involves checking that all eligibility criteria during the screening period have been met for randomization. Blood samples will be collected to test glucose concentrations after at least 4 hours of fasting as part of the safety laboratory evaluation. Abbreviations: 6MWT = 6-minute walk test; AE = adverse event; Cmax = maximum concentration; CMT-FOM = Charcot-Marie-Tooth Functional Outcome Measure; CMT-HI = Charcot-Marie-Tooth Health Index; CRF = case report form; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; EOT = end of treatment; FU = follow-up; HIV = human immunodeficiency virus; IMP = investigational medicinal product; IRT = interaction response technique; ONLS = global neuropathy limitation scale; PK = pharmacokinetics; SAE = serious adverse event; SF-36 = short form-36; sfEMG = single-fiber electromyography; SoA = schedule of activities; TUG = timed up-and-go test; V = visit; WOCBP = women of childbearing potential. [Figure 11C]Shows the schedule of activities during the clinical trial. Note: When possible, assessments should be conducted simultaneously at different visits. When possible, efficacy assessments should be conducted in the order listed in the SoA. Unscheduled visits may be conducted at any time. At unscheduled visits, all tests are optional and, if completed, should be reported on the CRF. Screening procedures may be conducted over several days within the 28-day screening period. The eligibility check conducted at the baseline visit involves checking that all eligibility criteria during the screening period have been met for randomization. Blood samples will be collected to test glucose concentrations after at least 4 hours of fasting as part of the safety laboratory evaluation. Abbreviations: 6MWT = 6-minute walk test; AE = adverse event; Cmax = maximum concentration; CMT-FOM = Charcot-Marie-Tooth Functional Outcome Measure; CMT-HI = Charcot-Marie-Tooth Health Index; CRF = case report form; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; EOT = end of treatment; FU = follow-up; HIV = human immunodeficiency virus; IMP = investigational medicinal product; IRT = interaction response technique; ONLS = global neuropathy limitation scale; PK = pharmacokinetics; SAE = serious adverse event; SF-36 = short form-36; sfEMG = single-fiber electromyography; SoA = schedule of activities; TUG = timed up-and-go test; V = visit; WOCBP = women of childbearing potential.

[0015] DETAILED DESCRIPTION OF THE INVENTION

[0016] definition All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0017] The nomenclature used in this application is based on IUPAC systematic nomenclature unless otherwise indicated.

[0018] The term "patient" or "subject" refers to a human (e.g., a male or female human) who has been diagnosed with Charcot-Marie-Tooth disease (CMT). CMT can be diagnosed through three different forms of testing: measuring nerve impulse velocity (nerve conduction studies), nerve biopsy, and DNA testing.

[0019] The term "improvement" refers to a reduction in the symptoms of Charcot-Marie-Tooth disease (CMT) in a patient when the patient is administered a composition described herein. The improvement can be a reduction in the patient's CMT symptoms after the patient is administered a composition described herein compared to before administration of the composition. The term "improvement" can also refer to a reduction in the CMT symptoms in a group of patients after the group of patients is administered a composition described herein, as assessed, for example, based on comparative test scores between the patient group administered a composition described herein and a control group receiving, for example, a placebo. Improvement in CMT symptoms may be measured, for example, by a decrease in the Overall Neuropathy Limitation Score (ONLS); an increase in total distance walked as determined using a 6-minute walk test; a reduction in fatigue as determined using a fatigue index calculated from the distance walked at minute 1 to the distance walked at minute 6 of a 6-minute walk test; a decrease in the CMT Neuropathy Score 2 (CMTNS2) score; a decrease in the CMT Examination Score (Second Version) (CMTES2) score; an increase in the Motor Function Index 32-item score; a decrease in the CMT Functional Outcome Measure (CMT-FOM) score; an increase in the Berg Balance Scale score; reduction in individualized neuromuscular quality of life scores; reduction in fatigue severity scale scores; reduction in jitter; reduction in blocking; improvement in manual dexterity as determined using the 9-hole peg test (9-HPT); improvement in walking ability as determined using the 6-spot step test; improvement in walking ability as determined using the 10 meter walk / run test; improvement in balance and mobility as determined using the timed "up and go" test; and may be determined as an increase in muscle strength assessed using a handheld dynamometer, a fixed dynamometer or manually, for example, using manual muscle testing.

[0020] The term "jitter" refers to the variability in arrival times of muscle fiber action potentials at the recording electrode between successive discharges when single fiber electromyography (sfEMG) is used to measure neuromuscular function.

[0021] The term "blocking" refers to the complete failure of NMJ transmission of muscle fiber action potentials to the recording electrode between successive discharges when sfEMG is used to measure neuromuscular function.

[0022] The term "placebo" refers to a dosage form that possesses no therapeutic activity.

[0023] The term "active pharmaceutical ingredient" (or "API") refers to a compound or molecule in a pharmaceutical composition that has a specific biological activity.

[0024] The terms "pharmaceutically acceptable excipient," "pharmaceutically acceptable carrier," and "therapeutically inactive excipient" are used interchangeably and may refer to any pharmaceutically acceptable ingredient in a pharmaceutical composition that has no therapeutic activity and is non-toxic to a subject to which it is administered, such as a disintegrant, binder, filler, solvent, buffer, tonicity agent, stabilizer, antioxidant, surfactant, carrier, diluent, or lubricant used in formulating a pharmaceutical product.

[0025] The term "pharmaceutical composition" refers to a preparation in which the biological activity of the active ingredient contained therein is effective and which does not contain additional ingredients that are unacceptably toxic to the subject to which the composition will be administered.

[0026] The term "pharmaceutically acceptable" refers to the attributes of a substance that is generally safe, non-toxic, not biologically or otherwise undesirable, and useful in preparing pharmaceutical compositions that are acceptable for veterinary and human pharmaceutical use.

[0027] A "pharmaceutically acceptable carrier" refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, that is non-toxic to a subject. Pharmaceutically acceptable carriers include, but are not limited to, buffering or acidifying agents, excipients, stabilizers, or preservatives.

[0028] The term "solid dosage form release" refers to the amount of compound released or dissolved into solution after a specified period of time when using a United States Pharmacopeia (USP) Type 2 dissolution apparatus in 900 mL of pH 6.8 phosphate / citrate buffer at a temperature of 37°C ± 0.5°C with a paddle speed of 75 rpm as described in Example 10.

[0029] The term “C max (expressed in units of ng / mL) refers to the maximum observed plasma concentration of NMD670. max " is an individual C max means the arithmetic mean of the values.

[0030] "T max ” (time unit or T in the study population) max (expressed as the median number of hours after drug administration) max If it occurs at multiple time points, T max is defined as the first time point with this value.

[0031] The term "dose" refers to the dose of NMD670 as the free acid given to a subject.

[0032] The term "dose" may also include NMD670 in combination with a pharmaceutically acceptable salt.

[0033] The term "therapeutically effective dose," as used herein, refers to the amount of NMD670 required to elicit a therapeutic response in a subject. The terms "therapeutically effective dose" and "therapeutic dose" are used interchangeably herein.

[0034] A composition comprising a (therapeutic) dose can be administered in one or more unit dosage forms. As used herein, "unit dosage form" refers to a physically separate unit suitable for human and animal subjects. Each unit dosage contains a predetermined amount of a therapeutically active compound, optionally associated with a pharmaceutical carrier, vehicle, or diluent. Examples of unit dosage forms include tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, ampoules and syringes, and oral solutions or suspensions, and oil-water emulsions. Unit dosage forms can be individually packaged, for example, in blister packs, as is known in the art. Unit dosage forms can be administered in fractions or multiples thereof.

[0035] The term “T 1 / 2 " (expressed in units of hours) refers to the terminal elimination half-life of NMD670 in plasma.

[0036] The term “AUC 0-無限大 ” (expressed in units of h ng / mL) means the cumulative area under the plasma time-concentration curve (AUC) calculated using the trapezoidal method from time 0 to infinity after a single dose of NMD670. The term “mean AUC 0-無限大 ” is the individual AUC 0-無限大 means the arithmetic mean of the values.

[0037] The term “AUC 0-24時間 ” (expressed in units of h ng / mL) means the cumulative area under the plasma time-concentration curve (AUC) calculated using the trapezoidal method from time 0 to 24 hours after a single dose of NMD670. The term “mean AUC 0-24時間 ” is the individual AUC 0~24時間 means the arithmetic mean of the values.

[0038] As used within the disclosure that follows, the term "NMD670" refers to (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, in addition to any pharmaceutically acceptable salts, hydrates, polymorphs, tautomers, or solvates thereof.

[0039] (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid according to the present disclosure refers to the compound of formula (I) below (CAS number 2354321-33-6):

[0040] [ka]

[0041] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0042] Detailed Description The CMT2D mouse model exhibits NMJ maturation defects, reduced endplate function, accelerated endplate functional decline during repetitive stimulation, and treatment efficacy with physostigmine, but not 3,4-DAP ( Sleigh et al., 2014 ; Spaulding et al., 2016 ).

[0043] Herein, we demonstrate that administration of the ClC-1 inhibitor NMD670 to isolated neuromuscular preparations from CMT2D mice resulted in higher endplate potentials (EPPs) and reduced excessive reductions in action potential firing during repeated stimulation of motor nerves compared to before compound administration (Figure 1). Furthermore, the percentage of action potentials not generated in response to stimulation of all measured fibers in each group per stimulation was reduced after addition of NMD670. This demonstrates that addition of ClC-1 inhibitors, particularly NMD670, to ex vivo muscle preparations can improve neuromuscular transmission in CMT2D mice. Furthermore, administration of ClC-1 inhibitors, particularly NMD670, to CMT2D mice resulted in increases in force, compound muscle action potentials (CMAPs), and relative force peaks (T4 or T10 / T1). This demonstrates that NMD670 can improve neuromuscular transmission, thereby restoring muscle function in vivo.

[0044] Herein, we further demonstrate that patients with CMT1 or CMT2 have significant NMJ transmission defects. Specifically, by measuring single-fiber electromyography (sfEMG), we found that blocking and jitter were higher in CMT patients compared with healthy age-matched controls (Figure 5). We also found that impairments in clinical parameters related to strength, balance, and mobility were correlated with jitter and blocking.

[0045] The discoveries provided by the above studies have enabled the inventors to develop compositions for use in CMT treatment methods and the CMT treatment methods described herein. Illustrative embodiments of these compositions and methods are provided below. The compositions and methods described herein are not intended to be limited to the following illustrative embodiments.

[0046] Compositions for use One embodiment of the present disclosure relates to compositions for use in a method for treating Charcot-Marie-Tooth disease in a subject, the method comprising administering to the patient a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid (NMD670), wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0047] Accordingly, one aspect of the present disclosure relates to a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, wherein the composition is for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0048] In exemplary embodiments, the therapeutically effective dose of NMD670 administered to a patient is less than 1500 mg, less than 1450 mg, less than 1300 mg, less than 1250 mg, less than 1200 mg, less than 1150 mg, less than 1100 mg, less than 1050 mg, less than 1000 mg, less than 950 mg, less than 900 mg, less than 850 mg, less than 800 mg, less than 750 mg, less than 700 mg, less than 650 mg, less than 600 mg, less than 550 mg, less than 500 mg, less than 450 mg, less than 400 mg, less than 350 mg, less than 300 mg, or less than 250 mg.

[0049] In other embodiments, the therapeutically effective dose of NMD670 administered to the patient is at least 100 mg, at least 150 mg, at least 200 mg, at least 250 mg, at least 300 mg, at least 350 mg, at least 400 mg, at least 450 mg, at least 500 mg, at least 550 mg, at least 600 mg, at least 650 mg, at least 700 mg, at least 750 mg, at least 800 mg, at least 850 mg, at least 900 mg, at least 950 mg, at least 1000 mg, at least 1050 mg, at least 1100 mg, at least 1150 mg, at least 1200 mg, at least 1250 mg, at least 1300 mg, at least 1350 mg, at least 1400 mg, or at least 1450 mg.

[0050] In some exemplary embodiments, the therapeutically effective dose of NMD670 administered to a patient is 100-600 mg, 200-600 mg, 250-550 mg, 300-500 mg, 350-450 mg, 375-425 mg, or 400 mg. In other exemplary embodiments, the therapeutically effective dose of NMD670 administered to a patient is 700-1400 mg, 800-1350 mg, 900-1300 mg, 1000-1250 mg, 1100-1250 mg, or about 1200 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 100 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 150 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 200 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 250 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 300 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 350 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 400 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 500 mg. In an exemplary embodiment, the therapeutically effective dose of NMD670 administered to a patient is about 600 mg.

[0051] In an exemplary embodiment, the therapeutic dose is administered at least once daily. In an exemplary embodiment, the therapeutic dose is administered once daily. In an exemplary embodiment, the therapeutic dose is administered twice daily. In an exemplary embodiment, the therapeutic dose is administered three times daily. In an exemplary embodiment, the therapeutic dose is administered four times daily.

[0052] In an exemplary embodiment, the therapeutic dose is administered once daily, i.e., the therapeutic dose is the total daily dosage. In an exemplary embodiment, the therapeutic dose is 100-600 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is 200-600 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is 300-500 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 100 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 150 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 200 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 250 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 300 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 350 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 400 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 500 mg and is administered once daily. In an exemplary embodiment, the therapeutic dose is about 600 mg and is administered once daily.

[0053] In an exemplary embodiment, the therapeutic dose is administered twice daily, i.e., the total daily dosage is twice the therapeutic dose. In an exemplary embodiment, the therapeutic dose is 100-600 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is 200-600 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is 300-500 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 100 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 150 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 200 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 250 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 300 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 350 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 400 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 500 mg and is administered twice daily. In an exemplary embodiment, the therapeutic dose is about 600 mg and is administered twice daily.

[0054] In an exemplary embodiment, the therapeutic dose is administered three times daily, i.e., the total daily dosage is three times the therapeutic dose. In an exemplary embodiment, the therapeutic dose is 100-600 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is 200-600 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is 300-500 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 100 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 150 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 200 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 250 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 300 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 350 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 400 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 500 mg and is administered three times daily. In an exemplary embodiment, the therapeutic dose is about 600 mg and is administered three times daily.

[0055] The composition containing the therapeutic dose can be administered in one or more unit dosage forms. For example, a 400 mg therapeutic dose can be administered as one unit dosage form containing 400 mg, or two unit dosage forms containing 200 mg, or four unit dosage forms containing 100 mg.

[0056] In an exemplary embodiment, the therapeutic dose is a total daily dosage.

[0057] In an exemplary embodiment, the composition for use is administered orally, i.e., the composition is for oral administration. In an exemplary embodiment, the composition for use is a solid dosage form. In an exemplary embodiment, the solid dosage form is administered orally. In an exemplary embodiment, the solid dosage form is selected from the group consisting of capsules (e.g., sprinkle capsules and gelatin capsules), tablets (e.g., uncoated tablets, coated tablets, slow-release tablets), and sprinkles. In an exemplary embodiment, the composition is in the form of a liquid, liquid suspension, oil, emulsion, or syrup. In an exemplary embodiment, the solid dosage form releases 80% or more of the compound after 30 minutes as measured in a United States Pharmacopeia (USP) Type 2 dissolution apparatus in 900 mL of pH 6.8 phosphate / citrate buffer at a temperature of 37°C ± 0.5°C with paddles at 75 rpm.

[0058] In an exemplary embodiment, the composition for use is orally administered using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, having a mean C max is 12,760 to 27,440 ng / mL, such as 15,000 to 25,000 ng / mL, for example, 16,000 to 24,000 ng / mL, for example, 16,080 to 25,125 ng / mL, such as 17,000 to 23,000 ng / mL, for example, 18,000 to 22,000 ng / mL, for example, 19,000 to 21,000 ng / mL, for example, about 20,100 ng / mL, after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the mean C max is 20,100 ng / mL, and the standard deviation is 7,340 ng / mL.

[0059] In an exemplary embodiment, the composition for use is orally administered using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, having a mean C max is about 80% to about 125%, e.g., 80.00% to 125.00%, of 20,100 ng / mL after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0060] In an exemplary embodiment, the composition for use is orally administered using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, comprising a mean AUC 0-無限大 is 66,300 to 109,100 h·ng / mL, for example, 70,000 to 105,000 h·ng / mL, for example, 70,160 to 109,625 h·ng / mL, for example, 75,000 to 100,000 h·ng / mL, for example, 80,000 to 95,000 h·ng / mL, for example, 85,000 to 90,000 h·ng / mL, for example, about 87,700 h·ng / mL, after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the mean AUC 0-無限大 is 87,700 ng / mL, with a standard deviation of 21,400 ng / mL.

[0061] In an exemplary embodiment, the composition for use is orally administered using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, comprising a mean AUC 0-無限大 is about 80% to about 125%, e.g., 80.00% to 125.00%, of 87,700 h after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0062] In an exemplary embodiment, the composition or use is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, that achieves a T within 1 to 6 hours after administration. max to reach.

[0063] In an exemplary embodiment, the composition or use is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, that achieves a Tmax of 1.0 within 3 to 7 hours after administration. max to reach.

[0064] In an exemplary embodiment, the AUC 0-24無限大 , C max or T max is measured after administration of a single dose to human subjects suffering from Charcot-Marie-Tooth disease.

[0065] Compositions for use as described herein may be formulated for administration either orally, parenterally, intravenously, by inhalation, topically, enterally, rectally, buccally or as an aerosol.

[0066] In an exemplary embodiment, the composition for use further comprises at least one pharmaceutically acceptable adjuvant and / or excipient. In an exemplary embodiment, the composition for use further comprises at least one pharmaceutically acceptable adjuvant and / or excipient selected from the group consisting of fillers, binders, lubricants, and disintegrants. In an exemplary embodiment, the composition for use comprises at least one pharmaceutically acceptable adjuvant and / or excipient selected from the group consisting of silicified microcrystalline cellulose, microcrystalline cellulose, maltodextrin, magnesium stearate, and croscarmellose sodium.

[0067] In an exemplary embodiment, the composition for use comprises 10-80 wt %, e.g., 40-65 wt %, e.g., 50-55 wt %, e.g., about 53 wt % (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0068] In an exemplary embodiment, the composition for use comprises 10-80 wt%, for example, 40-65 wt%, for example, 50-60 wt%, for example, 50-55 wt%, for example, 55-60 wt%, for example, about 53 wt%, for example, about 56 wt%, of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0069] In an exemplary embodiment, the composition for use comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; and e. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of a disintegrant in the form of one or more solid dosage forms, wherein the sum of the wt% of the ingredients does not exceed 100 wt%.

[0070] In an exemplary embodiment, the composition for use comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; e. 0.25 to 5 wt %, e.g., 0.3 to 2.5 wt %, of a disintegrant; and f. 1 to 10 wt% film coating in the form of one or more solid dosage forms, wherein the sum of the wt% of the ingredients does not exceed 100 wt%.

[0071] In an exemplary embodiment, the composition for use comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1-15 wt% maltodextrin, for example, 1.5-7 wt%, for example, 1.8-6.0 wt%; e. 0.25 to 3 wt %, for example, 0.4 to 2.0 wt % magnesium stearate; and f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt% croscarmellose sodium in the form of one or more solid dosage forms, wherein the sum of the wt% of the ingredients does not exceed 100 wt%.

[0072] In an exemplary embodiment, the composition for use is in the form of a solid dosage form, a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1-15 wt% maltodextrin, for example, 1.5-7 wt%, for example, 1.8-6.0 wt%; e. 0.25 to 3 wt %, for example, 0.4 to 2.0 wt % magnesium stearate; and f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt% croscarmellose sodium However, the total wt% of the components does not exceed 100 wt%.

[0073] In an exemplary embodiment, the composition for use comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-55 wt %, for example, about 53 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1-15 wt% maltodextrin, for example, 1.5-7 wt%, for example, 1.8-6.0 wt%; e. 0.25 to 3 wt %, for example, 0.4 to 2.0 wt % magnesium stearate; and f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt% croscarmellose sodium g. 1 to 10 wt. % of a film coating composition, such as Opadry White in the form of one or more solid dosage forms comprising or consisting of, provided that the sum of the wt% of the ingredients does not exceed 100 wt%.

[0074] In an exemplary embodiment, the composition for use is in the form of a solid dosage form, a. 10-80 wt %, for example, 40-65 wt %, for example, 50-55 wt %, for example, about 53 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1-15 wt% maltodextrin, for example, 1.5-7 wt%, for example, 1.8-6.0 wt%; e. 0.25-3 wt %, e.g., 0.4-2.0 wt % magnesium stearate; f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of croscarmellose sodium; and g. 1 to 10 wt. % of a film coating composition, such as Opadry White comprising or consisting of, provided that the sum of the wt% of the components does not exceed 100 wt%.

[0075] In an exemplary embodiment, the subject has a serum uric acid level of less than 6.5 mg / dL.

[0076] In an exemplary embodiment, the subject is diagnosed with CMTD. In an exemplary embodiment, the subject is diagnosed with CMT1. In an exemplary embodiment, the subject is diagnosed with CMT1A. In an exemplary embodiment, the subject is diagnosed with CMT1B. In an exemplary embodiment, the subject is diagnosed with CMT1C. In an exemplary embodiment, the subject is diagnosed with CMT1D. In an exemplary embodiment, the subject is diagnosed with CMT1E. In an exemplary embodiment, the subject is diagnosed with CMT1F. In an exemplary embodiment, the subject is diagnosed with CMT1G.

[0077] In an exemplary embodiment, the subject is diagnosed with CMT2. In an exemplary embodiment, the subject is diagnosed with CMT2A. In an exemplary embodiment, the subject is diagnosed with CMT2A1. In an exemplary embodiment, the subject is diagnosed with CMT2A2A. In an exemplary embodiment, the subject is diagnosed with CMT2A2B. In an exemplary embodiment, the subject is diagnosed with CMT2B. In an exemplary embodiment, the subject is diagnosed with CMT2B1. In an exemplary embodiment, the subject is diagnosed with CMT2B2. In an exemplary embodiment, the subject is diagnosed with CMT2C. In an exemplary embodiment, the subject is diagnosed with CMT2D. In an exemplary embodiment, the subject is diagnosed with CMT2E. In an exemplary embodiment, the subject is diagnosed with CMT2F. In an exemplary embodiment, the subject is diagnosed with CMT2H. In an exemplary embodiment, the subject is diagnosed with CMT2I. In an exemplary embodiment, the subject is diagnosed with CMT2J. In an exemplary embodiment, the subject is diagnosed with CMT2K. In an exemplary embodiment, the subject is diagnosed with CMT2L. In an exemplary embodiment, the subject is diagnosed with CMT2M. In an exemplary embodiment, the subject is diagnosed with CMT2N. In an exemplary embodiment, the subject is diagnosed with CMT2O. In an exemplary embodiment, the subject is diagnosed with CMT2P. In an exemplary embodiment, the subject is diagnosed with CMT2Q. In an exemplary embodiment, the subject is diagnosed with CMT2R. In an exemplary embodiment, the subject is diagnosed with CMT2S. In an exemplary embodiment, the subject is diagnosed with CMT2T. In an exemplary embodiment, the subject is diagnosed with CMT2U. In an exemplary embodiment, the subject is diagnosed with CMT2V. In an exemplary embodiment, the subject is diagnosed with CMT2Z. In an exemplary embodiment, the subject is diagnosed with CMT2X. In an exemplary embodiment, the subject is diagnosed with CMT2Y. In an exemplary embodiment, the subject is diagnosed with CMT2CC. In an exemplary embodiment, the subject is diagnosed with CMT2DD. In an exemplary embodiment, the subject has been diagnosed with CMT2EE.

[0078] In an exemplary embodiment, the subject has been diagnosed with CMT3.

[0079] In an exemplary embodiment, the subject is diagnosed with CMT4. In an exemplary embodiment, the subject is diagnosed with CMT4A. In an exemplary embodiment, the subject is diagnosed with CMT4B1. In an exemplary embodiment, the subject is diagnosed with CMT4B2. In an exemplary embodiment, the subject is diagnosed with CMT4B3. In an exemplary embodiment, the subject is diagnosed with CMT4C. In an exemplary embodiment, the subject is diagnosed with CMT4D. In an exemplary embodiment, the subject is diagnosed with CMT4E. In an exemplary embodiment, the subject is diagnosed with CMT4F. In an exemplary embodiment, the subject is diagnosed with CMT4G. In an exemplary embodiment, the subject is diagnosed with CMT4H. In an exemplary embodiment, the subject is diagnosed with CMT4J.

[0080] In an exemplary embodiment, the subject is diagnosed with CMTDI. In an exemplary embodiment, the subject is diagnosed with CMTDIA. In an exemplary embodiment, the subject is diagnosed with CMTDIB. In an exemplary embodiment, the subject is diagnosed with CMTDIC. In an exemplary embodiment, the subject is diagnosed with CMTDID. In an exemplary embodiment, the subject is diagnosed with CMTDIE. In an exemplary embodiment, the subject is diagnosed with CMTDIF.

[0081] In an exemplary embodiment, the subject has been diagnosed with CMTRI. In an exemplary embodiment, the subject has been diagnosed with CMTRIA. In an exemplary embodiment, the subject has been diagnosed with CMTRIB.

[0082] In an exemplary embodiment, the subject is diagnosed with CMTX1 (also called CMT1X). In an exemplary embodiment, the subject is diagnosed with CMTX2. In an exemplary embodiment, the subject is diagnosed with CMTX3. In an exemplary embodiment, the subject is diagnosed with CMTX4. In an exemplary embodiment, the subject is diagnosed with CMTX5. In an exemplary embodiment, the subject is diagnosed with CMTX6.

[0083] In exemplary embodiments, the subject has been diagnosed with CMT1, CMT2, or CMTX. In exemplary embodiments, the subject has been diagnosed with CMT1 or CMT2. In exemplary embodiments, the subject has been diagnosed with CMT1A, CMT1B, CMT2A, or CMTX1.

[0084] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered once daily. It relates to a composition.

[0085] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered once daily. It relates to a composition.

[0086] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily. It relates to a composition.

[0087] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily. It relates to a composition.

[0088] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered three times daily. It relates to a composition.

[0089] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered three times daily. It relates to a composition.

[0090] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered four times daily. It relates to a composition.

[0091] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered four times daily. It relates to a composition.

[0092] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered once daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0093] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0094] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered three times daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0095] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered four times daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0096] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered once daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0097] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0098] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered three times daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0099] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered four times daily; The composition is in the form of a solid dosage form and is administered orally. It relates to a composition.

[0100] In an exemplary embodiment, the subject experiences a reduction in symptoms of Charcot-Marie-Tooth disease.

[0101] In exemplary embodiments, subjects experience a reduction in overall neuropathy limitation score (ONLS) (Graham et al, 2006) after treatment with NMD670. In exemplary embodiments, the reduction in overall neuropathy limitation score can be determined by comparing the change from baseline in overall neuropathy limitation score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in overall neuropathy limitation score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a reduction in their global neuropathy limit score after treatment with NMD670, wherein the score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, such as 0.3 to 10 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0102] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in the global neuropathy limitation score. It relates to a composition.

[0103] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in the global neuropathy limitation score. It relates to a composition.

[0104] In an exemplary embodiment, a subject experiences an increase in total distance walked after treatment with NMD670. The increase in total distance walked can be determined using a 6-minute walk test (ATS, 2002). In an exemplary embodiment, an improvement in total distance walked can be determined by comparing the change from baseline in total distance walked after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in total distance walked after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject experiences an increase in total distance walked as determined using a 6-minute walk test after treatment with NMD670. In an exemplary embodiment, the subject experiences an increase in total distance walked as determined using a 6 minute walk test after treatment with NMD670, wherein the total distance walked is increased by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 5% and 400%, for example, between 5% and 200%, for example, between 10% and 200%. In an exemplary embodiment, the subject experiences an increase in total distance walked as determined using a 6 minute walk test after treatment with NMD670, wherein the total distance walked is an increase of at least 20 meters, such as at least 30 meters, for example, at least 40 meters, for example, at least 50 meters, for example, at least 60 meters, for example, at least 80 meters, for example, at least 100 meters, for example, at least 150 meters, for example, at least 200 meters, for example, at least 250 meters, for example, at least 300 meters, for example, 20 to 400 meters, for example, 30 to 300 meters, for example, 40 to 200 meters.

[0105] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an increase in total distance walked as determined using the 6-minute walk test, It relates to a composition.

[0106] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an increase in total distance walked as determined using the 6-minute walk test, It relates to a composition.

[0107] In an exemplary embodiment, a subject experiences reduced fatigue after treatment with NMD670, as determined using a fatigue index. The fatigue index is calculated from the distance walked at the first minute to the distance walked at the sixth minute of a six-minute walk test. In an exemplary embodiment, the reduction in fatigue can be determined by comparing the change from baseline in the fatigue index after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in the fatigue index after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a reduction in fatigue after treatment with NMD670 as determined using a fatigue index, wherein fatigue is reduced by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 40%, for example, at least 50%, for example, at least 60%, for example, at least 70%, for example, at least 80%, for example, between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%.

[0108] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a reduction in fatigue as determined using a fatigue index. It relates to a composition.

[0109] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a reduction in fatigue as determined using a fatigue index. It relates to a composition.

[0110] In an exemplary embodiment, a subject experiences a decrease in CMT Neuropathy Score 2 (CMTNS2) score after treatment with NMD670 (Murphy et al., 2011). In an exemplary embodiment, the decrease in CMTNS2 score can be determined by comparing the change from baseline in CMTNS2 score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in CMTNS2 score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject experiences a decrease in CMTNS2 score after treatment with NMD670, wherein the score is decreased by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, for example, at least 3 points, for example, at least 4 points, for example, at least 5 points, for example, at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, 0.3 to 20 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0111] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a reduction in CMT neuropathy score of 2 scores. It relates to a composition.

[0112] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a reduction in CMT neuropathy score of 2 scores. It relates to a composition.

[0113] In an exemplary embodiment, a subject experiences a decrease in CMTES2 score (second version) after treatment with NMD670 (Murphy et al., 2011). In an exemplary embodiment, the decrease in CMTES2 score can be determined by comparing the change from baseline in CMTES2 score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in CMTES2 score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject experiences a decrease in CMTES2 score after treatment with NMD670, wherein the score is decreased by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, for example, at least 3 points, for example, at least 4 points, for example, at least 5 points, for example, at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, 0.3 to 20 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0114] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in CMT test score (second version) score, It relates to a composition.

[0115] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in CMT test score (second version) score, It relates to a composition.

[0116] In an exemplary embodiment, a subject experiences an increase in a 32-item motor function index score after treatment with NMD670 (Allard et al., 2014). In an exemplary embodiment, the increase in the 32-item motor function index score can be determined by comparing the change from baseline in the 32-item motor function index score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in the 32-item motor function index score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject experiences an increase in the 32-item motor function index score after treatment with NMD670, wherein the score is increased by at least 5%, e.g., at least 10%, e.g., at least 15%, e.g., at least 20%, e.g., at least 25%, e.g., at least 30%, e.g., at least 40%, e.g., at least 50%, e.g., at least 60%, e.g., at least 70%, e.g., at least 80%, e.g., between 5% and 95%, e.g., between 5% and 80%, e.g., between 10% and 50%.

[0117] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects will experience an increase in scores on 32 motor function indexes. It relates to a composition.

[0118] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects will experience an increase in scores on 32 motor function indexes. It relates to a composition.

[0119] In an exemplary embodiment, subjects experience a decrease in CMT Functional Outcome Measure (CMT-FOM) score after treatment with NMD670 (Eichinger et al., 2018). In an exemplary embodiment, the decrease in CMT-FOM score can be determined by comparing the change from baseline in CMT-FOM score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in CMT-FOM score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a decrease in CMT-FOM score after treatment with NMD670, wherein the score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, such as at least 15 points, for example, at least 20 points, for example, between 0.3 and 30 points, for example, between 0.5 and 20 points, for example, between 0.3 and 10 points.

[0120] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in CMT functional outcome index score, It relates to a composition.

[0121] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in CMT functional outcome index score, It relates to a composition.

[0122] In an exemplary embodiment, the subject experiences an increase in Berg Balance Scale score after treatment with NMD670 (Berg et al., 1989). In an exemplary embodiment, the increase in Berg Balance Scale score can be determined by comparing the change from baseline in Berg Balance Scale score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in Berg Balance Scale score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences an increase in Berg Balance Scale score after treatment with NMD670, wherein the score increases by at least 0.5 points, such as at least 1 point, for example, at least 2 points, for example, at least 3 points, for example, at least 4 points, for example, at least 5 points, for example, at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, at least 15 points, for example, at least 20 points, for example, 0.5 to 30 points, for example, 1 to 20 points, for example, 0.5 to 10 points.

[0123] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an increase in Berg Balance Scale score, It relates to a composition.

[0124] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an increase in Berg Balance Scale score, It relates to a composition.

[0125] In exemplary embodiments, the subject experiences a decrease in their personalized neuromuscular quality of life score after treatment with NMD670 (Vincent et al., 2007). In exemplary embodiments, the decrease in personalized neuromuscular quality of life score can be determined by comparing the change from baseline in personalized neuromuscular quality of life score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in personalized neuromuscular quality of life score after a defined period (e.g., 21 days) of placebo treatment. In exemplary embodiments, the subject experiences a decrease in their personalized neuromuscular quality of life score after treatment with NMD670, the score decreasing by at least 0.5 points, such as at least 1 point, for example, at least 2 points, for example, at least 3 points, for example, at least 4 points, for example, at least 5 points, for example, at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, at least 15 points, for example, at least 20 points, for example, 0.5 to 30 points, for example, 1 to 20 points, for example, 0.5 to 10 points.

[0126] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in an individualized neuromuscular quality of life score. It relates to a composition.

[0127] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in an individualized neuromuscular quality of life score. It relates to a composition.

[0128] In an exemplary embodiment, the subject experiences a decrease in fatigue severity scale score after treatment with NMD670 (Krupp et al., 1989). In an exemplary embodiment, the decrease in fatigue severity scale score can be determined by comparing the change from baseline in fatigue severity scale score after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in fatigue severity scale score after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a decrease in fatigue severity scale score after treatment with NMD670, wherein the score is decreased by at least 0.5 points, such as at least 1 point, such as at least 2 points, such as at least 3 points, such as at least 4 points, such as at least 5 points, such as at least 6 points, such as at least 8 points, such as at least 10 points, such as at least 15 points, such as at least 20 points, such as 0.5 to 30 points, such as 1 to 20 points, such as 0.5 to 10 points.

[0129] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in fatigue severity scale score. It relates to a composition.

[0130] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences a decrease in fatigue severity scale score. It relates to a composition.

[0131] In an exemplary embodiment, a subject experiences a reduction in jitter after treatment with NMD670. In an exemplary embodiment, a subject experiences a reduction in jitter after treatment with NMD670, as determined using single-fiber electromyography (Sanders et al., 2019). In an exemplary embodiment, the reduction in jitter can be determined by comparing the change from baseline in jitter after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in jitter after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a reduction in jitter after treatment with NMD670 as determined using single fiber electromyography, wherein the jitter is reduced by at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%. In an exemplary embodiment, the subject experiences a reduction in jitter after treatment with NMD670 as determined using single fiber electromyography, wherein the jitter is reduced by at least 5 μs, such as at least 10 μs, for example, at least 15 μs, for example, at least 20 μs, for example, at least 25 μs, for example, at least 30 μs, for example, at least 40 μs, for example, at least 50 μs, for example, at least 75 μs, for example, at least 100 μs, such as between 5 μs and 200 μs, for example, between 5 μs and 100 μs, for example, between 10 μs and 50 μs.

[0132] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences a reduction in jitter as determined using single fiber electromyography; It relates to a composition.

[0133] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences a reduction in jitter as determined using single fiber electromyography; It relates to a composition.

[0134] In an exemplary embodiment, the subject experiences a reduction in blocking after treatment with NMD670. In an exemplary embodiment, the subject experiences a reduction in blocking after treatment with NMD670, as determined using single-fiber electromyography (Sanders et al., 2019). In an exemplary embodiment, the reduction in blocking can be determined by comparing the change from baseline in blocking after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in blocking after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences a reduction in blocking after treatment with NMD670 as determined using single fiber electromyography, wherein the blocking is reduced by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%.

[0135] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences a reduction in blocking as determined using single fiber electromyography; It relates to a composition.

[0136] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences a reduction in blocking as determined using single fiber electromyography; It relates to a composition.

[0137] In an exemplary embodiment, a subject experiences improved manual dexterity after treatment with NMD670. In an exemplary embodiment, a subject experiences improved manual dexterity after treatment with NMD670, as determined using the 9-hole peg test (9-HPT) (Svensson et al., 2006; Mathiowetz et al., 1985). In an exemplary embodiment, the improvement in manual dexterity can be determined by comparing the change from baseline in the time to complete the 9-HPT after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in the time to complete the 9-HPT after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences improved manual dexterity after treatment with NMD670, as determined using the 9-HPT, and the time to complete the 9-HPT is reduced by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, such as between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%.

[0138] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects experience improvement in manual dexterity as determined using the 9-hole peg test. It relates to a composition.

[0139] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects experience improvement in manual dexterity as determined using the 9-hole peg test. It relates to a composition.

[0140] In an exemplary embodiment, a subject experiences an improvement in walking ability after treatment with NMD670. In an exemplary embodiment, a subject experiences an improvement in walking ability after treatment with NMD670, as determined using the Six-Spot Step Test (SSST) (Nieuwenhuis et al, 2006). In an exemplary embodiment, the improvement in walking ability can be determined by comparing the time to complete the SSST after a defined period (e.g., 21 days) of NMD670 treatment with the time to complete the SSST after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences an improvement in walking ability after treatment with NMD670, as determined using the SSST, and the time to complete the SSST is reduced by at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, by 5% to 95%, for example, by 5% to 80%, for example, by 10% to 50%. In an exemplary embodiment, the subject experiences an improvement in walking ability after treatment with NMD670, as determined using the SSST, wherein the time to complete the SSST is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 and 10 seconds, for example, between 0.3 and 5 seconds, for example, between 0.5 and 5 seconds.

[0141] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences improvement in walking ability as determined using the 6-spot step test, It relates to a composition.

[0142] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences improvement in walking ability as determined using the 6-spot step test, It relates to a composition.

[0143] In an exemplary embodiment, a subject experiences improved walking ability after treatment with NMD670. In an exemplary embodiment, a subject experiences improved walking ability after treatment with NMD670, as determined using the 10-meter walk / run test (10MWRT) (Hiu et al., 2017; Krosschell et al., 2022). In an exemplary embodiment, the improvement in walking ability can be determined by comparing the time to complete the 10MWRT after a defined period (e.g., 21 days) of NMD670 treatment with the time to complete the 10MWRT after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences an improvement in walking ability after treatment with NMD670, as determined using a 10MWRT, and the time to complete the 10MWRT is reduced by at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, by 5% to 95%, for example, 5% to 80%, for example, 10% to 50%. In an exemplary embodiment, the subject experiences an improvement in walking ability after treatment with NMD670, as determined using a 10MWRT, and the time to complete the 10MWRT is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 and 10 seconds, for example, between 0.3 and 5 seconds, for example, between 0.5 and 5 seconds.

[0144] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an improvement in walking ability as determined using a 10 meter walk / run test, It relates to a composition.

[0145] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; The subject experiences an improvement in walking ability as determined using a 10 meter walk / run test, It relates to a composition.

[0146] In an exemplary embodiment, a subject experiences improved balance and mobility after treatment with NMD670. In an exemplary embodiment, a subject experiences improved balance and mobility after treatment with NMD670, as determined using the timed "up and go" (TUG) test (Podsiadlo et al., 1991). In an exemplary embodiment, the improvement in balance and mobility can be determined by comparing the time to complete the TUG test after a defined period (e.g., 21 days) of NMD670 treatment with the time to complete the TUG test after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, the subject experiences improvement in balance and mobility after treatment with NMD670, as determined using the TUG test, and the time to complete the TUG test is reduced by at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, by 5% to 95%, for example, by 5% to 80%, for example, by 10% to 50%. In an exemplary embodiment, the subject experiences improved balance and mobility after treatment with NMD670, as determined using the TUG test, and the time to complete the TUG test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 and 10 seconds, for example, between 0.3 and 5 seconds, for example, between 0.5 and 5 seconds.

[0147] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects experience improvements in balance and mobility as determined using a timed "up and go" test. It relates to a composition.

[0148] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; Subjects experience improvements in balance and mobility as determined using a timed "up and go" test. It relates to a composition.

[0149] In exemplary embodiments, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670. Grip strength is one indicator of muscle strength and can be used to determine the maximum force / tension generated by forearm muscles. Grip strength can be used as a screening tool for measuring upper body strength and whole body strength. In exemplary embodiments, an increase in muscle strength can also be determined by measuring the strength of the thigh (knee flexors), upper arm (elbow flexors and elbow extensors), and / or shoulder (shoulder abductors). In exemplary embodiments, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring grip strength using a handheld dynamometer (Febrer et al., 2010; Merlini et al., 2002). In exemplary embodiments, an increase in muscle strength can be determined by comparing the change from baseline in muscle strength after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in muscle strength after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring muscle strength using a handheld dynamometer, wherein muscle strength is increased by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 10% and 400%, for example, between 15% and 200%, for example, between 20% and 100%.

[0150] In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring grip strength using a handheld dynamometer, wherein grip strength is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, such as at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, such as at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, such as 0.25-5.0 kg, for example, 0.25-4.0 kg, for example, 0.5-4.0 kg.

[0151] In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670 as determined by measuring knee flexor strength using a handheld dynamometer, and grip strength is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, such as at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, such as at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, such as 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0152] In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670 as determined by measuring elbow flexor strength using a handheld dynamometer, and grip strength is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, such as at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, such as at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, such as 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0153] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences an increase in muscle strength as determined by measuring muscle strength using a handheld dynamometer, It relates to a composition.

[0154] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences an increase in muscle strength as determined by measuring muscle strength using a handheld dynamometer, It relates to a composition.

[0155] In exemplary embodiments, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670. In exemplary embodiments, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring muscle strength using a stationary dynamometer (e.g., an isokinetic dynamometer) (Anders et al., 2012; Harbo et al., 2012). In exemplary embodiments, the increase in muscle strength can be determined by comparing the change from baseline in muscle strength after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in muscle strength after a defined period (e.g., 21 days) of placebo treatment. In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring muscle strength using a stationary dynamometer, wherein muscle strength is increased by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 10% and 400%, for example, between 15% and 200%, for example, between 20% and 100%.

[0156] In an exemplary embodiment, a subject or group of subjects experiences an increase in muscle strength after treatment with NMD670, as determined by measuring ankle dorsiflexion muscle strength using a stationary dynamometer, wherein ankle dorsiflexion is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, such as at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, such as at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, for example, 0.25-5.0 kg, for example, 0.25-4.0 kg, for example, 0.5-4.0 kg.

[0157] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences an increase in isometric muscle strength as determined by measuring muscle strength using a stationary dynamometer, It relates to a composition.

[0158] In an exemplary embodiment, the disclosure provides a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising: The composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; The composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; the subject experiences an increase in isometric muscle strength as determined by measuring muscle strength using a stationary dynamometer, It relates to a composition.

[0159] In an exemplary embodiment, the present disclosure relates to a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, wherein the subject has a serum uric acid level of less than 6.5 mg / dL. In an exemplary embodiment, the composition for use is for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid. In an exemplary embodiment, the composition for use is for administration at a therapeutic dose as defined herein.

[0160] In one aspect, the present invention relates to the use of a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, in the manufacture of a medicament for the treatment of Charcot-Marie-Tooth disease in a subject, wherein the composition is for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0161] Pharmaceutical Compositions Another aspect of the present disclosure relates to a composition comprising a therapeutically effective dose of NMD670 for use in treating or ameliorating symptoms of Charcot-Marie-Tooth disease in a patient suffering from Charcot-Marie-Tooth disease. A further aspect of the present disclosure relates to a composition comprising a therapeutically effective dose of NMD670 in treating or ameliorating symptoms of Charcot-Marie-Tooth disease in a patient suffering from Charcot-Marie-Tooth disease. The following exemplary embodiments of compositions may be used in the methods of treatment described herein:

[0162] In one aspect, the present invention relates to a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In one embodiment, the composition comprises 50 to 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In one aspect, the present invention relates to a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, formulated as a solid dosage form, wherein the composition comprises 50 to 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid. In an exemplary embodiment, the composition further comprises at least one pharmaceutically acceptable adjuvant and / or excipient. In an exemplary embodiment, the composition is for oral administration. In an exemplary embodiment, the composition further comprises a pharmaceutically acceptable adjuvant and / or excipient selected from the group consisting of a filler, a binder, a lubricant, and a disintegrant. In an exemplary embodiment, the composition comprises a pharmaceutically acceptable adjuvant and / or excipient selected from the group consisting of silicified microcrystalline cellulose, microcrystalline cellulose, maltodextrin, magnesium stearate, and croscarmellose sodium.

[0163] In an exemplary embodiment, the composition contains 50 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition contains 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0164] In an exemplary embodiment, the composition comprises 10% to 80 wt%, e.g., 40 to 65 wt%, e.g., 50 to 55 wt%, e.g., about 53 wt%, of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the composition comprises 10% to 80 wt%, for example, 40 to 65 wt%, for example, 50 to 60 wt%, for example, 50 to 55 wt%, for example, 55 to 60 wt%, for example, about 53 wt%, for example, about 56 wt%, of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0165] In an exemplary embodiment, the composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; and e. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of a disintegrant However, the total wt% of the components does not exceed 100 wt%.

[0166] In an exemplary embodiment, the composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; e. 0.25 to 5 wt %, e.g., 0.3 to 2.5 wt %, of a disintegrant; and f. 1 to 10 wt% film coating However, the total wt% of the components does not exceed 100 wt%.

[0167] In an exemplary embodiment, the composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1 to 15 wt %, for example, 1.5 to 7 wt %, for example, 1.8 to 6.0 wt % maltodextrin; and e. 0.25 to 3 wt %, for example, 0.4 to 2.0 wt % magnesium stearate; and f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt% croscarmellose sodium However, the total wt% of the components does not exceed 100 wt%.

[0168] In an exemplary embodiment, the composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-55 wt %, for example, about 53 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1 to 15 wt %, for example, 1.5 to 7 wt %, for example, 1.8 to 6.0 wt % maltodextrin; and e. 0.25-3 wt %, e.g., 0.4-2.0 wt % magnesium stearate; f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of croscarmellose sodium; and g. 1 to 10 wt. % of a film coating composition, such as Opadry White comprising or consisting of, provided that the sum of the wt% of the components does not exceed 100 wt%.

[0169] In an exemplary embodiment, the disclosure relates to a composition comprising a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg.

[0170] In an exemplary embodiment, the present disclosure relates to a composition formulated as a solid dosage form comprising a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 50 mg to 400 mg. In an exemplary embodiment, the therapeutically effective dose is 100 mg. In an exemplary embodiment, the therapeutically effective dose is 150 mg. In an exemplary embodiment, the therapeutically effective dose is 200 mg. In an exemplary embodiment, the therapeutically effective dose is 250 mg. In an exemplary embodiment, the therapeutically effective dose is 300 mg. In an exemplary embodiment, the therapeutically effective dose is 350 mg. In an exemplary embodiment, the therapeutically effective dose is 400 mg. In an exemplary embodiment, the therapeutically effective dose is given once a given day. In an exemplary embodiment, the therapeutically effective dose is given two times per given day. In an exemplary embodiment, the therapeutically effective dose is given three times per given day. In an exemplary embodiment, the therapeutically effective dose is given four times per given day.

[0171] In an exemplary embodiment, the present disclosure relates to a composition formulated as a solid dosage form comprising 50 mg to 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the solid dosage form comprises 100 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 150 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 200 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 250 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 300 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 350 mg of NMD670. In an exemplary embodiment, the solid dosage form comprises 400 mg of NMD670.

[0172] In an exemplary embodiment, the composition is a solid dosage form. In an exemplary embodiment, the solid dosage form is selected from the group consisting of capsules (e.g., sprinkle capsules and gelatin capsules), tablets (e.g., uncoated tablets, coated tablets, slow-release tablets), and sprinkles. In an exemplary embodiment, the composition is in the form of a liquid, liquid suspension, oil, emulsion, or syrup. In an exemplary embodiment, the solid dosage form releases 80% or more of the compound after 30 minutes as measured in a United States Pharmacopeia (USP) Type 2 dissolution apparatus in 900 mL of pH 6.8 phosphate / citrate buffer at a temperature of 37°C ± 0.5°C with paddles at 75 rpm.

[0173] method In one aspect, the disclosure relates to a method of treating Charcot-Marie-Tooth disease in a subject, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0174] In an exemplary embodiment, a method for treating a patient suffering from symptoms of Charcot-Marie-Tooth disease includes a decrease in the overall neuropathy limitation score; an increase in the total distance walked during a 6-minute walk test; a reduction in fatigue as determined using a fatigue index calculated from a 6-minute walk test; a decrease in the CMT Neuropathy Score 2 score; a decrease in the CMT Examination Score (Second Version) score; an increase in the Motor Function Index 32-item score; a decrease in the CMT Functional Outcome Index score; an increase in the Berg Balance Scale score; a decrease in the Individualized Neuromuscular Quality of Life score; a decrease in the Fatigue Severity Scale score; and and / or improvement in neuromuscular junction transmission (improvement is reduced jitter and / or blocking as measured using sfEMG); improved manual dexterity as determined using the 9-hole peg test (9-HPT); improved walking ability as determined using the 6-spot step test; improved walking ability as determined using the 10-meter walk / run test; improved balance and mobility as determined using a timed "up and go" test; increased muscle strength as assessed with a handheld dynamometer; and / or increased muscle strength as assessed with a fixed dynamometer.

[0175] Accordingly, one aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in a reduction in the overall neuropathy limitation score (ONLS) in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. An improvement in the overall neuropathy limitation score (ONLS) is a reduction in the score (Graham et al., 2006).

[0176] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in an improvement in total distance walked in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in total distance walked can be determined using the 6-minute walk test (ATS, 2002).

[0177] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in reduced fatigue, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The reduction in fatigue can be calculated from the distance walked at the first minute to the distance walked at the sixth minute of the 6-minute walk test (ATS, 2002).

[0178] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in a reduction in a CMT Neuropathy Score 2 (CMTNS2) score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the CMT Neuropathy Score 2 score is a reduction in the score (Murphy et al., 2011).

[0179] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in a reduction in a CMT Test Score (Second Version) (CMTES2) score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the CMT Test Score (Second Version) score is a reduction in the score (Murphy et al., 2011).

[0180] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in an increase in a 32-item motor index score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the 32-item motor index score is an increase in the score (Allard et al., 2014).

[0181] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in a reduction in a CMT Functional Outcome Measure (CMT-FOM) score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the CMT Functional Outcome Measure score is a reduction in the score (Eichinger et al., 2018).

[0182] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in an increase in the Berg Balance Scale score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the Berg Balance Scale score is an increase in the score (Berg et al., 1989).

[0183] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in a reduction in a patient's personalized neuromuscular quality of life score, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in the personalized neuromuscular quality of life score is a reduction in the score (Vincent et al. 2007).

[0184] One embodiment of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease, resulting in a decrease in Fatigue Severity Scale score in a patient, the methods comprising administering to the patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in Fatigue Severity Scale score is a decrease in the score (Krupp et al., 1989).

[0185] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved neuromuscular junction transmission, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improved neuromuscular junction transmission can be a reduction in jitter and / or blocking, and can be determined using single-fiber electromyography (Sanders et al., 2019).

[0186] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved dexterity, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in dexterity can be determined using the 9-hole peg test (Svensson et al., 2006; Mathiowetz et al., 1985).

[0187] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved walking ability, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in walking ability can be determined using the 6-spot step test (Nieuwenhuis et al., 2006).

[0188] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved walking ability, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in walking ability can be determined using the 10-meter walk / run test (Hiu et al., 2017; Krosschell et al., 2022).

[0189] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved balance and mobility, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improvement in balance and mobility can be determined using the timed "up and go" test (Podsiadlo et al., 1991).

[0190] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved muscle strength, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. The improved muscle strength can be determined by measuring grip strength using a handheld dynamometer (Febrer et al., 2010; Merlini et al., 2002).

[0191] One aspect of the present disclosure relates to methods for treating Charcot-Marie-Tooth disease that result in improved muscle strength, the methods comprising administering to a patient a therapeutically effective dose of NMD670, wherein the therapeutic dose is in the range of 100 mg to 1500 mg. Improvements in muscle strength can be determined by measuring muscle strength using a stationary dynamometer (e.g., an isokinetic dynamometer) (Anders et al., 2012; Harbo et al., 2012).

[0192] In one aspect, the disclosure relates to a method for treating Charcot-Marie-Tooth disease in a subject in need thereof, comprising administering to the subject a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0193] In one aspect, the disclosure relates to a method for improving recovery of neuromuscular transmission and / or skeletal muscle function, comprising administering to the subject a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0194] In one aspect, the disclosure provides a method for treating Charcot-Marie-Tooth disease in a subject having a serum uric acid level greater than 6.5 mg / dL, the method comprising administering a low dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the subject until the patient's serum uric acid level is reduced to less than 6.5 mg / dL. and then administering to the subject a therapeutic dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the low dose is in the range of 20 mg to 150 mg, e.g., 25 mg to 100 mg, e.g., 25 mg to 50 mg, and the therapeutic dose is in the range of 200 mg to 1500 mg.

[0195] In an exemplary embodiment, the composition is administered at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0196] In an exemplary embodiment, the composition is administered at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0197] In an exemplary embodiment, the composition is administered at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0198] In an exemplary embodiment, the composition is administered at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0199] In an exemplary embodiment, the composition is administered at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0200] In an exemplary embodiment, the composition is administered at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0201] In an exemplary embodiment, the composition is administered at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0202] In an exemplary embodiment, the composition is administered at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0203] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0204] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0205] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0206] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0207] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0208] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0209] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0210] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0211] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0212] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0213] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0214] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0215] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0216] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0217] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0218] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0219] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0220] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0221] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0222] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0223] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0224] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0225] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0226] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0227] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0228] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times daily.

[0229] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0230] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0231] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0232] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once daily.

[0233] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice daily.

[0234] In an exemplary embodiment, the composition is administered at a therapeutic dose of about 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times daily.

[0235] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a decrease in global neuropathy limit score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences an improvement in overall neuropathy limitation score.

[0236] In an exemplary embodiment, the patient experiences a reduction in the global neuropathy restriction score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, for example, 0.3 to 10 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0237] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in an increase in total distance walked in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein, after administration of a therapeutically effective dose of the compound, the patient experiences an increase in total distance walked as determined using a 6-minute walk test.

[0238] In exemplary embodiments, improvement in total distance walked is determined by comparing the change from baseline in total distance walked after a defined period (e.g., 21 days) of NMD670 treatment with the change from baseline in total distance walked after a defined period (e.g., 21 days) of placebo treatment. In exemplary embodiments, the patient experiences an increase in total distance walked of at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 5% and 400%, for example, between 5% and 200%, for example, between 10% and 200%. In an exemplary embodiment, the patient experiences an increase in total distance walked of at least 20 meters, such as at least 30 meters, for example, at least 40 meters, for example, at least 50 meters, for example, at least 60 meters, for example, at least 80 meters, for example, at least 100 meters, for example, at least 150 meters, such as at least 200 meters, for example, at least 250 meters, for example, at least 300 meters, for example, from 20 to 400 meters, for example, from 30 to 300 meters, for example, from 40 to 200 meters.

[0239] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in reduced fatigue in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a reduction in fatigue as determined using a fatigue index calculated from the distance walked at minute 1 to the distance walked at minute 6 of a 6-minute walk test.

[0240] In exemplary embodiments, the patient experiences a reduction in fatigue of at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 40%, for example, at least 50%, for example, at least 60%, for example, at least 70%, for example, at least 80%, for example, between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%.

[0241] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a decrease in CMT Neuropathy Score 2 (CMTNS2) score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a decrease in CMTNS score.

[0242] In an exemplary embodiment, the patient experiences a reduction in CMTNS2 score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as 0.3 to 20 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0243] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a decrease in CMT Examination Score (Second Version) (CMTES2) score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a decrease in CMTES2 score.

[0244] In an exemplary embodiment, the patient experiences a reduction in CMTES2 score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, such as 0.3 to 20 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0245] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in an increase in a 32-item motor function index score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences an increase in the 32-item motor function index score.

[0246] In an exemplary embodiment, the patient experiences an increase in the 32-item motor function index score of at least 5%, e.g., at least 10%, e.g., at least 15%, e.g., at least 20%, e.g., at least 25%, e.g., at least 30%, e.g., at least 40%, e.g., at least 50%, e.g., at least 60%, e.g., at least 70%, e.g., at least 80%, e.g., 5% to 95%, e.g., 5% to 80%, e.g., 10% to 50%.

[0247] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a decrease in a CMT Functional Outcome Measure (CMT-FOM) score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg, and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a decrease in CMT-FOM score.

[0248] In an exemplary embodiment, the patient experiences a reduction in CMT-FOM score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, at least 15 points, such as at least 20 points, for example, between 0.3 and 30 points, for example, between 0.5 and 20 points, for example, between 0.3 and 10 points.

[0249] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in an increase in Berg Balance Scale score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences an increase in Berg Balance Scale score.

[0250] In an exemplary embodiment, the patient experiences an increase in Berg Balance Scale score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, for example, at least 15 points, such as at least 20 points, for example, between 0.3 and 30 points, for example, between 0.5 and 20 points, for example, between 0.3 and 10 points.

[0251] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a reduction in a personalized neuromuscular quality of life score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. maxwherein after administration of a therapeutically effective dose of the compound, the patient experiences a decrease in a personalized neuromuscular quality of life score.

[0252] In an exemplary embodiment, the patient experiences a decrease in their personalized neuromuscular quality of life score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, for example, at least 15 points, such as at least 20 points, for example, between 0.3 and 30 points, for example, between 0.5 and 20 points, for example, between 0.3 and 10 points.

[0253] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a decrease in Fatigue Severity Scale score in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a decrease in fatigue severity scale score.

[0254] In an exemplary embodiment, the patient experiences a reduction in Fatigue Severity Scale score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, for example, at least 15 points, such as at least 20 points, for example, between 0.3 and 30 points, for example, between 0.5 and 20 points, for example, between 0.3 and 10 points.

[0255] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in a reduction of jitter in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg, and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a reduction in jitter as determined using single fiber electromyography.

[0256] In exemplary embodiments, the patient experiences a reduction in jitter of at least 10%, such as at least 15%, such as at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, between 5% and 95%, for example, between 5% and 80%, for example, between 10% and 50%. In exemplary embodiments, the subject experiences a reduction in jitter of at least 5 μs, for example, at least 10 μs, for example, at least 15 μs, for example, at least 20 μs, for example, at least 25 μs, for example, at least 30 μs, for example, at least 40 μs, for example, at least 50 μs, for example, at least 75 μs, for example, at least 100 μs, for example, between 5 μs and 200 μs, for example, between 5 μs and 100 μs, for example, between 10 μs and 50 μs.

[0257] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in reduced blocking in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg, and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences a reduction in blocking as determined using single fiber electromyography.

[0258] In exemplary embodiments, the patient experiences a reduction in blocking of at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0259] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in improved manual dexterity in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences improved manual dexterity as determined using the 9-hole peg test.

[0260] In exemplary embodiments, the patient experiences an improvement in manual dexterity of at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, such as at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, such as 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0261] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in improved walking ability in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences an improvement in walking ability.

[0262] In exemplary embodiments, the patient experiences an improvement in walking ability of at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0263] In an exemplary embodiment, the patient experiences an improvement in walking ability and the time to complete the Six Spot Step Test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 seconds and 10 seconds, for example, between 0.3 seconds and 5 seconds, for example, between 0.5 seconds and 5 seconds.

[0264] In an exemplary embodiment, the patient experiences an improvement in walking ability and the time to complete a 10 meter walk / run test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 and 10 seconds, for example, between 0.3 and 5 seconds, for example, between 0.5 and 5 seconds.

[0265] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in improved balance and mobility in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient.max wherein after administration of a therapeutically effective dose of the compound, the patient experiences improved balance and mobility.

[0266] In exemplary embodiments, the patient experiences an improvement in balance and mobility of at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0267] In an exemplary embodiment, the patient experiences an improvement in walking ability, and the time to complete a timed "up and go" test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as between 0.3 seconds and 10 seconds, for example, between 0.3 seconds and 5 seconds, for example, between 0.5 seconds and 5 seconds.

[0268] In one aspect, the disclosure provides a method of treating Charcot-Marie-Tooth disease, resulting in increased muscle strength in a patient in need thereof, the method comprising administering a therapeutically effective dose of the compound (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutically effective dose is in the range of 100 mg to 1500 mg and results in a C of 2,790 ng / mL to 76,700 ng / mL in the patient. max wherein after administration of a therapeutically effective dose of the compound, the patient experiences an increase in muscle strength.

[0269] In exemplary embodiments, the patient experiences an increase in muscle strength of at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, for example, from 10% to 400%, for example, from 15% to 200%, for example, from 20% to 100%.

[0270] In an exemplary embodiment, the patient experiences an increase in muscle strength as determined by measuring grip strength using a handheld dynamometer, and grip strength increases by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, for example, 0.25-5.0 kg, for example, 0.25-4.0 kg, for example, 0.5-4.0 kg.

[0271] In an exemplary embodiment, the patient experiences an increase in muscle strength as determined by measuring ankle dorsiflexion muscle strength using a stationary dynamometer, and the ankle dorsiflexion strength increases by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, for example, 0.25-5.0 kg, for example, 0.25-4.0 kg, for example, 0.5-4.0 kg.

[0272] In an exemplary embodiment, a therapeutically effective dose of the compound is orally administered to a patient. In an exemplary embodiment, the therapeutically effective dose is in the range of 100 mg to 600 mg. In an exemplary embodiment, the therapeutically effective dose is in the range of 200 mg to 600 mg. In an exemplary embodiment, the therapeutically effective dose is 100 mg. In an exemplary embodiment, the therapeutically effective dose is 150 mg. In an exemplary embodiment, the therapeutically effective dose is 200 mg. In an exemplary embodiment, the therapeutically effective dose is 250 mg. In an exemplary embodiment, the therapeutically effective dose is 300 mg. In an exemplary embodiment, the therapeutically effective dose is 350 mg. In an exemplary embodiment, the therapeutically effective dose is 400 mg. In an exemplary embodiment, the therapeutically effective dose is 500 mg. In an exemplary embodiment, the therapeutically effective dose is 600 mg. In an exemplary embodiment, the therapeutically effective dose is administered once, twice, three times, or four times daily.

[0273] The disclosed methods may further include administering a second therapeutically effective dose of NMD670 to the patient either 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or at least 7 days after the first therapeutically effective dose is administered. The second therapeutically effective dose of NMD670 may range from 100 mg to about 1500 mg. In exemplary embodiments, the second therapeutically effective dose of NMD670 is any dosage disclosed herein. In other embodiments, the second therapeutically effective dose of NMD670 is the same as the first therapeutically effective dose administered to the patient.

[0274] In other exemplary embodiments, the methods of the present disclosure further comprise administering to the patient a third therapeutically effective dose of NMD670 either 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or at least 7 days after the second therapeutically effective dose is administered. The third therapeutically effective dose of NMD670 can range from 100 mg to about 1500 mg. In exemplary embodiments, the third therapeutically effective dose of NMD670 is any dosage disclosed herein. In other embodiments, the third therapeutically effective dose of NMD670 is the same as the first therapeutically effective dose and / or the second therapeutically effective dose administered to the patient.

[0275] In some exemplary embodiments, administration of a therapeutically effective dose of NMD670 is repeated at least 1, 2, 3, 4, 5, or 6 times weekly. In other exemplary embodiments, administration is repeated at least 1-3 times weekly, 2-5 times weekly, or 3-6 times weekly.

[0276] In some exemplary embodiments, administration of a therapeutically effective dose of NMD670 is repeated daily. Administration of a therapeutically effective dose of NMD670 can be repeated, for example, 1, 2, 3, 4, 5, 6, 7, or 8 times daily. In other embodiments, administration is repeated 1 to 8 times daily or 2 to 5 times daily.

[0277] In some embodiments, the therapeutically effective dose of NMD670 is administered at least once daily. In an exemplary embodiment, the therapeutically effective dose of NMD670 is administered once daily.

[0278] In other embodiments, a therapeutically effective dose of NMD670 is administered either twice daily, three times daily, or four times daily.

[0279] In exemplary embodiments, the therapeutically effective dose of NMD670 is 100-600 mg, 300-500 mg, or about 400 mg administered once daily. In exemplary embodiments, the therapeutically effective dose of NMD670 is 200-600 mg, 300-500 mg, or about 400 mg administered once daily.

[0280] In other exemplary embodiments, the therapeutically effective dose of NMD670 is 100-600 mg, 300-500 mg, or about 400 mg administered twice daily. In other exemplary embodiments, the therapeutically effective dose of NMD670 is 200-600 mg, 300-500 mg, or about 400 mg administered twice daily.

[0281] In other exemplary embodiments, the therapeutically effective dose of NMD670 is 100-600 mg, 300-500 mg, or about 400 mg administered three times per day. In other exemplary embodiments, the therapeutically effective dose of NMD670 is 200-600 mg, 300-500 mg, or about 400 mg administered three times per day.

[0282] In other exemplary embodiments, the therapeutically effective dose of NMD670 is 100-600 mg, 300-500 mg, or about 400 mg administered four times per day. In other exemplary embodiments, the therapeutically effective dose of NMD670 is 200-600 mg, 300-500 mg, or about 400 mg administered four times per day.

[0283] In some exemplary embodiments, the therapeutically effective dose of NMD670 is a daily dosage of NMD670. In these embodiments, the daily dosage of NMD670 can be administered as a single dosage or in smaller dosages throughout the day. That is, in some embodiments, the daily dosage of NMD670 is administered either once a day or at least once a day, twice a day or at least two different times throughout the day, or three times a day or at least three different times throughout the day.

[0284] In other exemplary embodiments, the patient receiving a therapeutically effective dose of NMD670 does not have hyperuricemia. For example, the patient receiving a therapeutically effective dose of NMD670 has a serum uric acid level of less than 6.5 mg / dL. Patients with serum uric acid levels greater than 6.5 mg / dL may not be suitable for receiving a therapeutically effective dose. In exemplary embodiments in which the patient has a serum uric acid level greater than 6.5 mg / dL, the treatment method may further include administering a low dose of NMD670 until the patient's serum uric acid level drops to less than 6.5 mg / dL. The low dose of NMD670 may be between 20 mg and 150 mg, e.g., between 25 mg and 100 mg, e.g., between 25 mg and 50 mg. Once the patient's serum uric acid level drops to less than 6.5 mg / dL, they may begin receiving a therapeutically effective dose of NMD670.

[0285] Kit of Parts In one aspect, the present invention provides a method for producing a medicament for the treatment of a pulmonary arthritis, comprising: (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and Peripheral myelin protein 22 (PMP22) down-regulator Kit of parts including:

[0286] In an exemplary embodiment, the kit-of-parts contains 100-1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the PMP22 downregulator is PXT3003 (a combination of (RS)-baclofen, naltrexone hydrochloride, and D-sorbitol). In an exemplary embodiment, the PMP22 downregulator is a non-viral DNA plasmid, e.g., Engensis (VM202).

[0287] In one aspect, the present invention relates to (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and a peripheral myelin protein 22 (PMP22) downregulator for use in the treatment of Charcot-Marie-Tooth disease.

[0288] In one aspect, the present invention relates to a method for the treatment of Charcot-Marie-Tooth disease, comprising administering (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and a peripheral myelin protein 22 (PMP22) downregulator to a subject in need thereof.

[0289] In one aspect, the present invention relates to the use of a kit-of-parts or composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and a peripheral myelin protein 22 (PMP22) downregulator for the manufacture of a medicament for the treatment of Charcot-Marie-Tooth disease.

[0290] In one aspect, the present invention provides a method for producing a medicament for the treatment of a pulmonary arthritis, comprising: (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and Biotin or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof Kit of parts including:

[0291] In an exemplary embodiment, the kit of parts includes 100-1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof. In an exemplary embodiment, the kit of parts includes 100-300 mg of biotin (MD1003).

[0292] In other exemplary embodiments, the kit-of-parts further comprises one or more additional compounds, such as IFB-088, donor perminogen ceritinib, iselguastat, CKD-510, AGT-100216, MiM-111, EN-001, DTx-1252, lycorinstat, AT-007 (govorestat), reldesemtib, and / or pyridostigmine.

[0293] In one embodiment, the kit-of-parts is for use in a method of treating Charcot-Marie-Tooth disease in a subject.

[0294] item 1. A composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, said composition being for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0295] 2. The composition for use according to item 1, wherein said therapeutic dose is less than 1500 mg, such as less than 1450 mg, for example less than 1300 mg, for example less than 1250 mg, for example less than 1200 mg, such as less than 1150 mg, for example less than 1100 mg, for example less than 1050 mg, such as less than 1000 mg, for example less than 950 mg, such as less than 900 mg, for example less than 850 mg, for example less than 800 mg, such as less than 750 mg, for example less than 700 mg, such as less than 650 mg, for example less than 600 mg, such as less than 550 mg, for example less than 500 mg, such as less than 450 mg, for example less than 400 mg, for example less than 350 mg, for example less than 300 mg, such as less than 250 mg.

[0296] 3. The therapeutic dose may be at least 100 mg, such as at least 150 mg, for example, at least 200 mg, for example, at least 250 mg, for example, at least 300 mg, such as at least 350 mg, for example, at least 400 mg, for example, at least 450 mg, such as at least 500 mg, for example, at least 550 mg, for example, at least 600 mg, for example, at least 650 mg, for example, at least 700 mg, for example, at least 750 mg, for example, at least 800 mg, e.g. The composition for use according to any one of the preceding items, for example, at least 850 mg, such as at least 900 mg, for example, at least 950 mg, for example, at least 1000 mg, such as at least 1050 mg, for example, at least 1100 mg, for example, at least 1150 mg, such as at least 1200 mg, for example, at least 1250 mg, such as at least 1300 mg, for example, at least 1350 mg, such as at least 1400 mg, for example, at least 1450 mg.

[0297] 4. The composition for use according to item 1, wherein the therapeutic dose is 200 to 600 mg, for example, 250 to 550 mg, for example, 300 to 500 mg, for example, 350 to 450 mg, for example, 375 to 425 mg, for example, 400 mg.

[0298] 5. The composition for use according to item 1, wherein the therapeutic dose is 700 to 1400 mg, for example, 800 to 1350 mg, for example, 900 to 1300 mg, for example, 1000 to 1250 mg, for example, 1100 to 1250 mg, for example, about 1200 mg.

[0299] 6. The composition for use according to item 1, wherein the therapeutic dose is about 100 mg.

[0300] 7. The composition for use according to item 1, wherein the therapeutic dose is about 150 mg.

[0301] 8. The composition for use according to item 1, wherein the therapeutic dose is about 200 mg.

[0302] 9. The composition for use according to item 1, wherein the therapeutic dose is about 250 mg.

[0303] 10. The composition for use according to item 1, wherein the therapeutic dose is about 300 mg.

[0304] 11. The composition for use according to item 1, wherein the therapeutic dose is about 350 mg.

[0305] 12. The composition for use according to item 1, wherein the therapeutic dose is about 400 mg.

[0306] 13. The composition for use according to item 1, wherein the therapeutic dose is about 500 mg.

[0307] 14. The composition for use according to item 1, wherein the therapeutic dose is about 600 mg.

[0308] 15. The composition for use according to any one of the preceding items, wherein the therapeutic dose is administered at least once daily.

[0309] 16. The composition for use according to any one of the preceding items, wherein the therapeutic dose is administered once daily.

[0310] 17. The composition for use according to any one of items 1 to 15, wherein the therapeutic dose is administered twice a day.

[0311] 18. The composition for use according to any one of items 1 to 15, wherein the therapeutic dose is administered three times a day.

[0312] 19. The composition for use according to any one of items 1 to 15, wherein the therapeutic dose is administered four times a day.

[0313] 20. The composition for use according to item 1, wherein the therapeutic dose is 100 to 600 mg and the composition is administered once a day.

[0314] 21. The composition for use according to item 1, wherein the therapeutic dose is 200 to 600 mg and the composition is administered once a day.

[0315] 22. The composition for use according to item 1, wherein the therapeutic dose is 300 to 500 mg and the composition is administered once a day.

[0316] 23. The composition for use according to item 1, wherein the therapeutic dose is about 100 mg and the composition is administered once a day.

[0317] 24. The composition for use according to item 1, wherein the therapeutic dose is about 150 mg and the composition is administered once a day.

[0318] 25. The composition for use according to item 1, wherein the therapeutic dose is about 200 mg and the composition is administered once a day.

[0319] 26. The composition for use according to item 1, wherein the therapeutic dose is about 250 mg and the composition is administered once a day.

[0320] 27. The composition for use according to item 1, wherein the therapeutic dose is about 300 mg and the composition is administered once a day.

[0321] 28. The composition for use according to item 1, wherein the therapeutic dose is about 350 mg and the composition is administered once a day.

[0322] 29. The composition for use according to item 1, wherein the therapeutic dose is about 400 mg and the composition is administered once a day.

[0323] 30. The composition for use according to item 1, wherein the therapeutic dose is about 500 mg and the composition is administered once a day.

[0324] 31. The composition for use according to item 1, wherein the therapeutic dose is about 600 mg and the composition is administered once a day.

[0325] 32. The composition for use according to item 1, wherein the therapeutic dose is 100 to 600 mg and the composition is administered twice a day.

[0326] 33. The composition for use according to item 1, wherein the therapeutic dose is 200 to 600 mg and the composition is administered twice a day.

[0327] 34. The composition for use according to any one of items 1 to 5, wherein the therapeutic dose is 300 to 500 mg and the composition is administered twice a day.

[0328] 35. The composition for use according to item 1, wherein the therapeutic dose is about 100 mg and the composition is administered twice a day.

[0329] 36. The composition for use according to item 1, wherein the therapeutic dose is about 150 mg and the composition is administered twice a day.

[0330] 37. The composition for use according to item 1, wherein the therapeutic dose is about 200 mg and the composition is administered twice a day.

[0331] 38. The composition for use according to item 1, wherein the therapeutic dose is about 250 mg and the composition is administered twice a day.

[0332] 39. The composition for use according to item 1, wherein the therapeutic dose is about 300 mg and the composition is administered twice a day.

[0333] 40. The composition for use according to item 1, wherein the therapeutic dose is about 350 mg and the composition is administered twice a day.

[0334] 41. The composition for use according to item 1, wherein the therapeutic dose is about 400 mg and the composition is administered twice a day.

[0335] 42. The composition for use according to item 1, wherein the therapeutic dose is about 500 mg and the composition is administered twice a day.

[0336] 43. The composition for use according to item 1, wherein the therapeutic dose is about 600 mg and the composition is administered twice a day.

[0337] 44. The composition for use according to item 1, wherein the therapeutic dose is 100 to 600 mg and the composition is administered three times a day.

[0338] 45. The composition for use according to item 1, wherein the therapeutic dose is 200 to 600 mg and the composition is administered three times a day.

[0339] 46. ​​The composition for use according to item 1, wherein the therapeutic dose is 300 to 500 mg and the composition is administered three times a day.

[0340] 47. The composition for use according to item 1, wherein the therapeutic dose is about 100 mg and the composition is administered three times a day.

[0341] 48. The composition for use according to item 1, wherein the therapeutic dose is about 150 mg and the composition is administered three times a day.

[0342] 49. The composition for use according to item 1, wherein the therapeutic dose is about 200 mg and the composition is administered three times a day.

[0343] 50. The composition for use according to item 1, wherein the therapeutic dose is about 250 mg and the composition is administered three times a day.

[0344] 51. The composition for use according to item 1, wherein the therapeutic dose is about 300 mg and the composition is administered three times a day.

[0345] 52. The composition for use according to item 1, wherein the therapeutic dose is about 350 mg and the composition is administered three times a day.

[0346] 53. The composition for use according to item 1, wherein the therapeutic dose is about 400 mg and the composition is administered three times a day.

[0347] 54. The composition for use according to item 1, wherein the therapeutic dose is about 500 mg and the composition is administered three times a day.

[0348] 55. The composition for use according to item 1, wherein the therapeutic dose is about 600 mg and the composition is administered three times a day.

[0349] 56. The composition for use according to item 1, wherein the therapeutic dose is 100 to 600 mg and the composition is administered four times a day.

[0350] 57. The composition for use according to item 1, wherein the therapeutic dose is 200 to 600 mg and the composition is administered four times a day.

[0351] 58. A composition for use according to any one of items 1 to 5, wherein the therapeutic dose is a total daily dosage.

[0352] 59. A composition for use according to any one of the preceding items, wherein the composition is administered orally, parenterally, intravenously, by inhalation, topically, enterally, rectally, buccally or as an aerosol.

[0353] 60. The composition for use according to any one of items 1 to 59, wherein the composition is in the form of a liquid, a liquid suspension, an oil, an emulsion, or a syrup.

[0354] 61. A composition for use according to any one of items 1 to 59, wherein the composition is in solid dosage form.

[0355] 62. The composition for use according to item 61, wherein the solid dosage form is administered orally.

[0356] 63. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 100 to 600 mg, and the composition is administered once a day.

[0357] 64. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 200 to 600 mg, and the composition is administered once a day.

[0358] 65. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 100 to 600 mg, and the composition is administered twice a day.

[0359] 66. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 200 to 600 mg, and the composition is administered twice a day.

[0360] 67. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 100 to 600 mg, and the composition is administered three times a day.

[0361] 68. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 200 to 600 mg, and the composition is administered three times a day.

[0362] 69. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 100 to 600 mg, and the composition is administered four times a day.

[0363] 70. A composition for use according to any one of items 1 to 62, wherein the composition is in the form of a solid dosage form and is administered orally, the therapeutic dose is 200 to 600 mg, and the composition is administered four times a day.

[0364] 71. The composition for use according to any of items 61 to 70, wherein the solid dosage form is selected from the group consisting of capsules (e.g., sprinkle capsules and gelatin capsules), tablets (e.g., uncoated tablets, coated tablets, slow-release tablets) and sprinkles.

[0365] 72. The composition for use according to any of items 61 to 71, wherein the solid dosage form releases 80% or more of the compound after 30 minutes as measured in a United States Pharmacopoeia (USP) Type 2 dissolution apparatus in 900 mL of pH 6.8 phosphate / citrate buffer at a temperature of 37°C ± 0.5°C with paddles at 75 rpm.

[0366] 73. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a T 1 -T 2 -T 3 -T 4 -T 5 -T 6 -H 2 O 3 -T 1 -T 2 ... max 2. A composition for use according to any one of the preceding items, wherein the composition reaches

[0367] 74. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, with a T of 1 to 5 hours, e.g., 1.5 to 4 hours, e.g., about 2 hours or about 3 hours after administration. max 2. A composition for use according to any one of the preceding items, wherein the composition reaches

[0368] 75. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a T 1 concentration-time profile within 3 to 7 hours after administration. max 2. A composition for use according to any one of the preceding items, wherein the composition reaches

[0369] 76. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a mean C maxis 12,760 to 27,440 ng / mL, such as 15,000 to 25,000 ng / mL, for example, 16,000 to 24,000 ng / mL, such as 16,080 to 25,125 ng / mL, for example, 17,000 to 23,000 ng / mL, such as 18,000 to 22,000 ng / mL, for example, 19,000 to 21,000 ng / mL, such as about 20,100 ng / mL after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0370] 77. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the mean C max 77. The composition for use according to item 76, wherein the mean serum albumin concentration is 20,100 ng / mL and the standard deviation is 7,340 ng / mL.

[0371] 78. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a mean C max is about 80% to about 125%, e.g., 80.00% to 125.00%, of 20,100 ng / mL after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0372] 79. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a mean AUC 0-無限大 is 66,300 to 109,100 h ng / mL, such as 70,000 to 105,000 h ng / mL, for example 70,160 to 109,625 h ng / mL, such as 75,000 to 100,000 h ng / mL, for example 80,000 to 95,000 h ng / mL, such as 85,000 to 90,000 h ng / mL, for example about 87,700 h ng / mL, after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0373] 80. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a mean AUC 0-無限大 Item 10. The composition for use according to any one of the preceding items, wherein the saturation level is 87,700 ng / mL and the standard deviation is 21,400 ng / mL.

[0374] 81. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and provides a mean AUC 0-無限大is about 80% to about 125%, e.g., 80.00% to 125.00%, of 87,700 h ng / mL after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0375] 82. AUC 0-24 , AUC 無限大 , C max or T max Item 11. The composition for use according to any of the preceding items, wherein the IL-16 expression level is measured after administration of a single dose to a human subject suffering from Charcot-Marie-Tooth disease.

[0376] 83. A composition for use according to any one of the preceding items, wherein the composition further comprises at least one pharmaceutically acceptable adjuvant and / or excipient.

[0377] 84. The composition for use according to item 83, wherein the pharmaceutically acceptable adjuvants and / or excipients are selected from the group consisting of fillers, binders, lubricants and disintegrants.

[0378] 85. The composition for use according to item 83, wherein the pharmaceutically acceptable adjuvant and / or excipient is selected from the group consisting of silicified microcrystalline cellulose, microcrystalline cellulose, maltodextrin, magnesium stearate and croscarmellose sodium.

[0379] 86. A composition for use according to any of items 61 to 85, wherein the composition comprises 10 to 80 wt%, for example 40 to 65 wt%, for example 50 to 55 wt%, for example about 53 wt% of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0380] 87. A composition for use according to any of items 61 to 85, wherein the composition comprises 10 to 80 wt%, for example, 40 to 65 wt%, for example, 50 to 60 wt%, for example, 50 to 55 wt%, for example, 55 to 60 wt%, for example, about 53 wt%, for example, 56 wt% of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

[0381] 88. The composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; and e. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of a disintegrant 86. The composition for use according to any of items 61 to 85, comprising:

[0382] 89. The composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1-15 wt% maltodextrin, for example, 1.5-7 wt%, for example, 1.8-6.0 wt%; e. 0.25 to 3 wt %, for example, 0.4 to 2.0 wt % magnesium stearate; and f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt% croscarmellose sodium 86. The composition for use according to any of items 61 to 85, comprising:

[0383] 90. The composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-60 wt %, for example, 50-55 wt %, for example, 55-60 wt %, for example, about 53 wt %, for example, about 56 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 20-80 wt%, e.g., 25-50 wt%, of filler; c. 2-20 wt%, e.g., 3-16 wt%, of binder; d. 0.25 to 3 wt %, e.g., 0.4 to 2.0 wt %, of a lubricant; e. 0.25 to 5 wt %, e.g., 0.3 to 2.5 wt %, of a disintegrant; and f. 1 to 10 wt% film coating 86. The composition for use according to any one of items 61 to 85, comprising:

[0384] 91. The composition comprises: a. 10-80 wt %, for example, 40-65 wt %, for example, 50-55 wt %, for example, about 53 wt % of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof; b. 5-60 wt%, e.g., 20-40 wt%, e.g., 21-37 wt% silicified microcrystalline cellulose; c. 2-60 wt%, e.g., 5-16 wt%, microcrystalline cellulose; d. 1 to 15 wt %, for example, 1.5 to 7 wt %, for example, 1.8 to 6.0 wt % maltodextrin; and e. 0.25-3 wt %, e.g., 0.4-2.0 wt % magnesium stearate; f. 0.25 to 5 wt%, for example, 0.3 to 2.5 wt%, of croscarmellose sodium; and g. 1 to 10 wt. % of a film coating composition, such as Opadry White 86. A composition for use according to any of items 61 to 85, comprising or consisting of, with the proviso that the sum of said wt% of components does not exceed 100 wt%.

[0385] 92. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 100 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally once daily.

[0386] 93. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 200 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally once daily.

[0387] 94. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 100 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally twice daily.

[0388] 95. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 200 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally twice daily.

[0389] 96. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 100 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally three times a day.

[0390] 97. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 200 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally three times a day.

[0391] 98. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 100 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally four times a day.

[0392] 99. A composition for use according to any one of the preceding items, wherein the therapeutic dose is 200 to 600 mg, and the composition is in the form of a solid dosage form and is administered orally four times a day.

[0393] 100. A composition for use according to any one of the preceding items, wherein the composition is administered as one or more unit dosage forms.

[0394] 101. The composition for use according to any one of the preceding items, wherein the subject has a serum uric acid level of less than 6.5 mg / dL.

[0395] 102. A composition for use according to any one of the preceding items, wherein the subject experiences a reduction in symptoms of Charcot-Marie-Tooth disease.

[0396] 103. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences an increase in total distance walked as determined using a 6-minute walk test after treatment with the composition.

[0397] 104. The composition for use according to item 103, wherein the increase in total distance walked is determined by comparing the change from baseline in the total distance walked after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the total distance walked after a defined period of placebo treatment.

[0398] 105. The composition for use according to item 104, wherein the period is 21 days.

[0399] 106. The composition for use according to any one of items 103 to 105, wherein the total distance walked is increased by at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, such as at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, such as at least 100%, for example at least 150%, for example at least 200%.

[0400] 107. The composition for use according to any one of items 103 to 105, wherein the total distance walked is increased by 5% to 400%, for example, by 5% to 200%, for example, by 10% to 200%.

[0401] 108. The composition for use according to any one of items 103 to 105, wherein the total distance walked is increased by at least 20 meters, such as at least 30 meters, for example at least 40 meters, for example at least 50 meters, such as at least 60 meters, for example at least 80 meters, for example at least 100 meters, such as at least 150 meters, for example at least 200 meters, for example at least 250 meters, for example at least 300 meters.

[0402] 109. The composition for use according to any one of items 103 to 105, wherein the total distance walked is increased by 20 to 400 meters, for example, 30 to 300 meters, for example, 40 to 200 meters.

[0403] 110. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in total distance walked as determined using a 6-minute walk test.

[0404] 111. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in total distance walked as determined using a 6-minute walk test.

[0405] 112. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences an increase in muscle strength after treatment with the composition.

[0406] 113. The composition for use according to item 112, wherein the muscle strength is measured using a handheld dynamometer.

[0407] 114. The composition for use according to item 112, wherein the muscle strength is measured using a stationary dynamometer.

[0408] 115. The composition for use according to any one of items 112 or 113, wherein the muscle strength is measured as grip strength.

[0409] 116. The composition for use according to any one of items 112 or 113, wherein the muscle strength is measured as strength of the thigh (knee flexors), upper arm (elbow flexors and elbow extensors) and / or shoulder (shoulder abduction).

[0410] 117. A composition for use according to any one of items 112 or 114, wherein the muscle strength is measured as ankle dorsiflexion strength.

[0411] 118. The composition for use according to any one of items 112 to 117, wherein the increase in muscle strength is determined by comparing the change from baseline in muscle strength after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in muscle strength after a defined period of placebo treatment.

[0412] 119. The composition for use according to item 118, wherein the period is 21 days.

[0413] 120. The composition for use according to any one of the preceding items, wherein the muscle strength is increased by at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%.

[0414] 121. A composition for use according to any one of the preceding items, wherein the muscle strength is increased by 10% to 400%, for example, 15% to 200%, for example, 20% to 100%.

[0415] 122. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring grip strength using a handheld dynamometer, is increased by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, such as at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%.

[0416] 123. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring grip strength using a handheld dynamometer, is increased by 10% to 400%, for example, 15% to 200%, for example, 20% to 100%.

[0417] 124. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring grip strength using a handheld dynamometer, is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg.

[0418] 125. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring grip strength using a handheld dynamometer, is increased by 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0419] 126. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring knee flexor strength using a handheld dynamometer, is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, such as at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg.

[0420] 127. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring knee flexor strength using a handheld dynamometer, is increased by 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0421] 128. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring elbow flexor strength using a handheld dynamometer, is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, such as at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg.

[0422] 129. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring elbow flexor strength using a handheld dynamometer, is increased by 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0423] 130. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in muscle strength as determined by measuring grip strength using a handheld dynamometer.

[0424] 131. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in muscle strength as determined by measuring grip strength using a handheld dynamometer.

[0425] 132. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring ankle dorsiflexion muscle strength using a stationary dynamometer, is increased by at least 0.25 kg, such as at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, such as at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg.

[0426] 133. A composition for use according to any one of the preceding items, wherein the muscle strength, as determined by measuring ankle dorsiflexion muscle strength using a fixed dynamometer, is increased by 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0427] 134. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in isometric muscle strength as determined by measuring isometric muscle strength using a stationary dynamometer.

[0428] 135. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in isometric muscle strength as determined by measuring isometric muscle strength using a stationary dynamometer.

[0429] 136. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in overall neuropathy limitation score (ONLS) after treatment with the composition.

[0430] 137. The composition for use according to item 136, wherein the Overall Neuropathy Limitation Score (ONLS) is determined by comparing the change from baseline in the reduction of the Overall Neuropathy Limitation Score (ONLS) after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the reduction of the Overall Neuropathy Limitation Score (ONLS) after a defined period of placebo treatment.

[0431] 138. The composition for use according to item 137, wherein the period is 21 days.

[0432] 139. A composition for use according to any one of the preceding items, wherein the overall neuropathy limitation score (ONLS) is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points.

[0433] 140. A composition for use according to any one of the preceding items, wherein the overall neuropathy limitation score (ONLS) is decreased or increased by 0.3 to 10 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0434] 141. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in overall neuropathy limitation score (ONLS).

[0435] 142. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in overall neuropathy limitation score (ONLS).

[0436] 143. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences improved manual dexterity after treatment with the composition.

[0437] 144. The composition for use according to item 143, wherein the improvement in manual dexterity is determined using the 9-hole peg test (9-HPT).

[0438] 145. The composition for use according to item 144, wherein the improvement in manual dexterity is determined by comparing the change from baseline in the 9-hole peg test after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the 9-hole peg test after a defined period of placebo treatment.

[0439] 146. The composition for use according to item 145, wherein the period is 21 days.

[0440] 147. The composition for use according to any one of the preceding items, wherein said manual dexterity as determined using the 9-hole peg test is increased by at least 5%, such as at least 10%, for example at least 15%, such as at least 20%, for example at least 25%, such as at least 30%, for example at least 50%, such as at least 75%, for example at least 100%, such as at least 150%, for example at least 200%.

[0441] 148. The composition for use of any one of the preceding items, wherein the manual dexterity, as determined using the 9-hole peg test, is increased by 5% to 400%, such as by 10% to 300%, for example, by 10% to 200%.

[0442] 149. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences improved manual dexterity as determined using the 9-hole peg test.

[0443] 150. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences improved manual dexterity as determined using the 9-hole peg test.

[0444] 151. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in CMT Neuropathy Score 2 (CMTNS2) score after treatment with the composition.

[0445] 152. The composition for use according to item 151, wherein the reduction in the CMTNS2 score is determined by comparing the change from baseline in the reduction in the CMTNS2 score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the reduction in the CMTNS2 score after a defined period of placebo treatment.

[0446] 153. The composition for use according to item 152, wherein the period is 21 days.

[0447] 154. A composition for use according to any one of the preceding items, wherein the CMTNS2 score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points.

[0448] 155. A composition for use according to any one of the preceding items, wherein the CMTNS2 score is reduced by 0.3 to 20 points, for example, by 0.5 to 6 points, for example, by 0.3 to 5 points.

[0449] 156. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in CMT neuropathy score 2 score.

[0450] 157. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in CMT neuropathy score 2 score.

[0451] 158. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in CMT Test Score (Second Version) (CMTES2) score after treatment with the composition.

[0452] 159. The composition for use according to item 158, wherein the reduction in the CMTES2 score is determined by comparing the change from baseline in the reduction in the CMTES2 score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the reduction in the CMTES2 score after a defined period of placebo treatment.

[0453] 160. The composition for use according to item 159, wherein the period is 21 days.

[0454] 161. A composition for use according to any one of the preceding items, wherein the CMTES2 score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points.

[0455] 162. A composition for use according to any one of the preceding items, wherein the CMTES2 score is reduced by 0.3 to 20 points, for example, by 0.5 to 6 points, for example, by 0.3 to 5 points.

[0456] 163. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in CMT test score (second version) score.

[0457] 164. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in CMT test score (second version) score.

[0458] 165. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences reduced fatigue after treatment with the composition.

[0459] 166. The composition for use according to item 165, wherein the reduction in fatigue is determined using a fatigue index calculated from the distance walked in the first minute to the distance walked in the sixth minute of a 6-minute walking test.

[0460] 167. The composition for use according to item 166, wherein the reduction in fatigue is determined by comparing the change from baseline in the fatigue index after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in dropout rate in the fatigue index after a defined period of placebo treatment.

[0461] 168. The composition for use according to item 167, wherein the period is 21 days.

[0462] 169. A composition for use according to any one of the preceding items, wherein the reduction in fatigue, as determined using a fatigue index, is at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, for example at least 40%, for example at least 50%, for example at least 60%, for example at least 70%, for example at least 80%.

[0463] 170. A composition for use according to any one of the preceding items, wherein the reduction in fatigue, as determined using a fatigue index, is reduced by 5% to 95%, for example, by 5% to 80%, for example, by 10% to 50%.

[0464] 171. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in fatigue as determined using a fatigue index.

[0465] 172. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in fatigue as determined using a fatigue index.

[0466] 173. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences an increase in a 32-item motor function index score after treatment with the composition.

[0467] 174. The composition for use according to item 173, wherein the increase in the 32-item motor function index score is determined by comparing the change from baseline in the 32-item motor function index score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the 32-item motor function index score after a defined period of placebo treatment.

[0468] 175. The composition for use according to item 174, wherein the period is 21 days.

[0469] 176. A composition for use according to any one of the preceding items, wherein the 32-item motor function index score is increased by at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 40%, for example, at least 50%, for example, at least 60%, for example, at least 70%, for example, at least 80%.

[0470] 177. A composition for use according to any one of the preceding items, wherein the 32-item motor function index score is increased by 5% to 95%, for example, by 5% to 80%, for example, by 10% to 50%.

[0471] 178. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in a 32-item motor function index score.

[0472] 179. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in a 32-item motor function index score.

[0473] 180. The composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in CMT Functional Outcome Measure (CMT-FOM) score after treatment with the composition.

[0474] 181. The composition for use according to item 180, wherein the reduction in CMT-FOM score is determined by comparing the change from baseline in the reduction in CMT-FOM score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the reduction in CMT-FOM score after a defined period of placebo treatment.

[0475] 182. The composition for use according to item 181, wherein the period is 21 days.

[0476] 183. A composition for use according to any one of the preceding items, wherein the CMT-FOM score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, such as at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, for example, at least 15 points, for example, at least 20 points.

[0477] 184. A composition for use according to any one of the preceding items, wherein the CMT-FOM score is reduced by 0.3 to 30 points, for example, by 0.5 to 20 points, for example, by 0.3 to 10 points.

[0478] 185. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in a CMT Functional Outcome Index score.

[0479] 186. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in a CMT Functional Outcome Index score.

[0480] 187. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in Fatigue Severity Scale score after treatment with the composition.

[0481] 188. The composition for use according to item 187, wherein the reduction in the fatigue severity scale score is determined by comparing the change from baseline in the fatigue severity scale score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the fatigue severity scale score after a defined period of placebo treatment.

[0482] 189. The composition for use according to item 188, wherein the period is 21 days.

[0483] 190. The composition for use according to any one of items 187 to 189, wherein the fatigue severity scale score is reduced by 0.5 points, such as at least 0.75 points, for example at least 1 point, such as at least 1.5 points, for example at least 2 points, such as at least 3 points, for example at least 4 points, such as at least 5 points, for example at least 6 points, such as at least 8 points, for example at least 10 points, such as at least 15 points, for example at least 20 points.

[0484] 191. The composition for use according to any one of items 187 to 190, wherein the fatigue severity scale score is reduced by 1 to 20 points, for example, by 0.5 to 10 points.

[0485] 192. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in fatigue severity scale score.

[0486] 193. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in fatigue severity scale score.

[0487] 194. The composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a decrease in an individualized neuromuscular quality of life score after treatment with the composition.

[0488] 195. The composition for use according to item 194, wherein the reduction in the personalized neuromuscular quality of life score is determined by comparing the change from baseline in the personalized neuromuscular quality of life score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the personalized neuromuscular quality of life score after a defined period of placebo treatment.

[0489] 196. The composition for use according to item 195, wherein the period is 21 days.

[0490] 197. The composition for use according to any one of the preceding items, wherein the individualised neuromuscular quality of life score is reduced by 0.5 points, such as at least 0.75 points, for example, at least 1 point, for example, at least 1.5 points, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, such as at least 10 points, for example, at least 15 points, for example, at least 20 points.

[0491] 198. A composition for use according to any one of the preceding items, wherein the individualized neuromuscular quality of life score is reduced by 0.5 to 30 points, for example, 1 to 20 points, for example, 0.5 to 10 points.

[0492] 199. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in an individualized neuromuscular quality of life score.

[0493] 200. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a decrease in an individualized neuromuscular quality of life score.

[0494] 201. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences a reduction in jitter after treatment with the composition.

[0495] 202. The composition for use according to item 201, wherein the jitter is determined using single fiber electromyography.

[0496] 203. The composition for use according to any one of items 201 or 202, wherein the reduction in jitter is determined by comparing the change from baseline in the jitter after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the jitter after a defined period of placebo treatment.

[0497] 204. The composition for use according to item 203, wherein the period is 21 days.

[0498] 205. A composition for use according to any one of items 201 to 204, wherein the jitter is reduced by at least 10%, such as at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%.

[0499] 206. A composition for use according to any one of items 201 to 204, wherein the jitter is reduced by 5% to 95%, for example, by 5% to 80%, for example, by 10% to 50%.

[0500] 207. A composition for use according to any one of items 201 to 204, wherein the jitter determined using single fiber electromyography is reduced by at least 5 μs, such as at least 10 μs, for example at least 15 μs, such as at least 20 μs, for example at least 25 μs, such as at least 30 μs, for example at least 40 μs, such as at least 50 μs, for example at least 75 μs, for example at least 100 μs.

[0501] 208. A composition for use according to any one of items 201 to 204, wherein the jitter determined using single fiber electromyography is reduced by 5 μs to 200 μs, for example by 5 μs to 100 μs, for example by 10 μs to 50 μs.

[0502] 209. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in jitter as determined using single fiber electromyography.

[0503] 210. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in jitter as determined using single fiber electromyography.

[0504] 211. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences reduced blocking after treatment with the composition.

[0505] 212. The composition for use according to item 211, wherein the blocking is determined using single fiber electromyography.

[0506] 213. The composition for use according to any one of items 211 or 212, wherein the reduction in blocking is determined by comparing the change from baseline in blocking after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in blocking after a defined period of placebo treatment.

[0507] 214. The composition for use according to item 213, wherein the period is 21 days.

[0508] 215. A composition for use according to any one of items 211 to 214, wherein the blocking is reduced by at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%.

[0509] 216. A composition for use according to any one of items 211 to 215, wherein the blocking is reduced by 5% to 95%, for example by 5% to 80%, for example by 10% to 50%.

[0510] 217. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in blocking as determined using single fiber electromyography.

[0511] 218. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences a reduction in blocking as determined using single fiber electromyography.

[0512] 219. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences an increase in Berg Balance Scale score after treatment with the composition.

[0513] 220. The composition for use according to item 219, wherein the increase in the Berg Balance Scale score is determined by comparing the change from baseline in the Berg Balance Scale score after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the Berg Balance Scale score after a defined period of placebo treatment.

[0514] 221. The composition for use according to item 220, wherein the period is 21 days.

[0515] 222. The composition for use according to any one of items 220 to 221, wherein the Berg Balance Scale score is increased by 0.5 points, such as at least 1 point, for example at least 2 points, for example at least 3 points, such as at least 4 points, for example at least 5 points, such as at least 6 points, for example at least 8 points, for example at least 10 points, such as at least 15 points, for example at least 20 points.

[0516] 223. A composition for use according to any one of items 220 to 222, wherein the Berg Balance Scale score is increased by 0.5 to 30 points, for example, 1 to 20 points, for example, 0.5 to 10 points.

[0517] 224. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in Berg Balance Scale score.

[0518] 225. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an increase in Berg Balance Scale score.

[0519] 226. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences an improvement in walking ability after treatment with the composition.

[0520] 227. The composition for use according to item 226, wherein the walking ability is determined using the Six Spot Step Test (SSST).

[0521] 228. The composition for use according to any one of items 226 or 227, wherein the improvement in SSST walking performance is determined by comparing the time to complete the SSST after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, with the change from baseline in the time to complete the SSST after a defined period of placebo treatment.

[0522] 229. The composition for use according to item 228, wherein the period is 21 days.

[0523] 230. A composition for use according to any one of items 226 to 229, wherein the time to complete the SSST is reduced by at least 10%, such as at least 15%, for example at least 20%, such as at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, such as at least 100%, for example at least 150%, for example at least 200%.

[0524] 231. A composition for use according to any one of items 226 to 229, wherein the time to complete the SSST is reduced by 5% to 95%, for example by 5% to 80%, for example by 10% to 50%.

[0525] 232. The composition for use according to any one of items 226 to 229, wherein the time to complete the SSST is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example at least 0.7 seconds, such as at least 1.0 seconds, for example at least 1.5 seconds, such as at least 2 seconds, for example at least 2.5 seconds, such as at least 3 seconds, for example at least 4 seconds, for example at least 5 seconds.

[0526] 233. A composition for use according to any one of items 226 to 229, wherein the time to complete the SSST is reduced by 0.3 seconds to 10 seconds, for example, by 0.3 seconds to 5 seconds, for example, by 0.5 seconds to 5 seconds.

[0527] 234. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an improvement in walking ability as determined using a six-spot step test.

[0528] 235. The composition for use of any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an improvement in walking ability as determined using a six-spot step test.

[0529] 236. The composition for use according to item 169, wherein the walking ability is determined using the 10-meter walk / run test (10MWRT).

[0530] 237. The composition for use according to item 236, wherein the improvement in walking ability is determined by comparing the change from baseline in the 10MWRT after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the 10MWRT after a defined period of placebo treatment.

[0531] 238. The composition for use according to item 237, wherein the period is 21 days.

[0532] 239. A composition for use according to any one of items 237 or 238, wherein the time to complete the 10MWRT is reduced by at least 10%, such as at least 15%, for example at least 20%, such as at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, such as at least 100%, for example at least 150%, for example at least 200%.

[0533] 240. A composition for use according to any one of items 237 or 238, wherein the time to complete the 10MWRT is reduced by 5% to 95%, such as by 5% to 80%, for example by 10% to 50%.

[0534] 241. A composition for use according to any one of items 237 or 238, wherein the time to complete the 10MWRT is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example at least 0.7 seconds, such as at least 1.0 seconds, for example at least 1.5 seconds, such as at least 2 seconds, for example at least 2.5 seconds, such as at least 3 seconds, for example at least 4 seconds, for example at least 5 seconds.

[0535] 242. A composition for use according to any one of items 237 or 238, wherein the time to complete the 10MWRT is reduced by 0.3 seconds to 10 seconds, for example, by 0.3 seconds to 5 seconds, for example, by 0.5 seconds to 5 seconds.

[0536] 243. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an improvement in walking ability as determined using a 10-meter walk / run test.

[0537] 244. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences an improvement in walking ability as determined using a 10-meter walk / run test.

[0538] 245. A composition for use according to any one of the preceding items, wherein the subject or group of subjects experiences improved balance and mobility after treatment with the composition.

[0539] 246. The composition for use according to item 245, wherein the improvement in balance and mobility is determined by comparing the change from baseline in the timed "up and go" (TUG) test after a defined period of treatment with the composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, to the change from baseline in the TUG test after a defined period of placebo treatment.

[0540] 247. The composition for use according to item 246, wherein the period is 21 days.

[0541] 248. A composition for use according to any one of items 245 to 247, wherein the time to complete the TUG test is reduced by at least 10%, such as at least 15%, for example at least 20%, such as at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, such as at least 100%, for example at least 150%, for example at least 200%.

[0542] 249. A composition for use according to any one of items 245 to 247, wherein the time to complete the TUG test is reduced by 5% to 95%, for example by 5% to 80%, for example by 10% to 50%.

[0543] 250. The composition for use according to any one of items 245 to 247, wherein the time to complete the TUG test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example at least 0.7 seconds, such as at least 1.0 seconds, for example at least 1.5 seconds, such as at least 2 seconds, for example at least 2.5 seconds, such as at least 3 seconds, for example at least 4 seconds, for example at least 5 seconds.

[0544] 251. A composition for use according to any one of items 245 to 247, wherein the time to complete the TUG test is reduced by 0.3 seconds to 10 seconds, for example by 0.3 seconds to 5 seconds, for example by 0.5 seconds to 5 seconds.

[0545] 252. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences improvement in balance and mobility as determined using a timed "up and go" test.

[0546] 253. A composition for use according to any one of the preceding items, wherein the composition is for administration at a therapeutic dose of 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; the composition is administered twice daily; the composition is in the form of a solid dosage form and is administered orally; and the subject experiences improvement in balance and mobility as determined using a timed "up and go" test.

[0547] 254. A composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, wherein the subject has a serum uric acid level of less than 6.5 mg / dL.

[0548] 255. The composition for use according to item 254, wherein the composition is for administration in a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0549] 256. A method for treating Charcot-Marie-Tooth disease in a subject, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0550] 257. The method comprises: a.Decrease in overall neuropathy limitation score; b. Increase in total distance walked during the 6-minute walk test; c. Reduction in fatigue as determined using a fatigue index calculated from a 6-minute walk test; d. CMT neuropathy score 2-score decrease; e. Decrease in CMT test score (second version); f. Increase in the 32-item motor function index score; g. Reduction in CMT functional outcome index scores; h. Increased Berg Balance Scale score; i. A decrease in the individualized neuromuscular quality of life score; j. Decrease in fatigue severity scale score; k.Improvement of neuromuscular junction transmission; l. Improved manual dexterity as determined using the 9-Hole Peg Test (9-HPT); Improved walking ability as determined using the m.6 spot step test; n.Improvement in walking ability as determined using a 10-meter walk / run test; o. Improved balance and mobility as determined using a timed "up and go" test; p. Increased muscle strength as assessed by a handheld dynamometer; and / or q. Increased muscle strength as assessed by a stationary dynamometer Item 256. The method of claim 256,

[0551] 258. The method described in item 257, wherein the improvement in neuromuscular junction transmission is an improvement and a reduction in jitter and / or blocking when measured using sfEMG.

[0552] 259. A method for treating Charcot-Marie-Tooth disease in a subject resulting in an increase in total distance walked, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0553] 260. The method of item 259, wherein the increase in total distance walked is determined using a 6-minute walk test.

[0554] 261. The therapeutically effective dose is a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 261. The method according to one of items 259 or 260, wherein

[0555] 262. The method of one of items 259 to 261, wherein the improvement in total distance walked is determined by comparing the change from baseline in the total distance walked after a defined period of treatment with the composition to the change from baseline in the total distance walked after a defined period of placebo treatment.

[0556] 262. The method according to one of items 259 to 261, wherein the subject experiences an increase in total distance walked of at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%.

[0557] 263. The method according to one of items 260 or 262, wherein the subject experiences an increase in total distance walked of between 5% and 400%, such as between 5% and 200%, such as between 10% and 200%.

[0558] 264. The method of one of items 260 or 262, wherein the subject experiences an increase in total distance walked of at least 20 meters, such as at least 30 meters, for example at least 40 meters, for example at least 50 meters, such as at least 60 meters, for example at least 80 meters, for example at least 100 meters, for example at least 150 meters, such as at least 200 meters, for example at least 250 meters, for example at least 300 meters.

[0559] 265. The method according to one of items 260 or 262, wherein the subject experiences an increase in total distance walked of 20 to 400 meters, such as 30 to 300 meters, such as 40 to 200 meters.

[0560] 266. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in increased muscle strength gain, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0561] 267. The method described in item 266, wherein the increase in muscle strength is determined by measuring the strength of the thigh (knee flexors), upper arm (elbow flexors and elbow extensors) and / or shoulder (shoulder abductors) or by measuring grip strength.

[0562] 268. The method according to one of items 266 to 267, wherein the strength is determined by measuring grip strength using a handheld dynamometer.

[0563] 269. The method according to one of items 266 to 268, wherein the strength is determined by measuring muscle strength using a stationary dynamometer.

[0564] 270. The method according to one of items 266 to 269, wherein the subject experiences an increase in muscle strength of at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, such as at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, such as at least 200%, for example from 10% to 400%, for example from 15% to 200%, for example from 20% to 100%.

[0565] 271. The method of one of items 266 to 270, wherein the subject experiences an increase in muscle strength as determined by measuring grip strength using a handheld dynamometer, and the grip strength is increased by at least 0.25 kg, for example, at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, for example, 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0566] 272. The method of one of items 266 to 271, wherein the subject experiences an increase in muscle strength as determined by measuring grip strength using a handheld dynamometer, and the grip strength is increased by at least 0.25 kg, for example, at least 0.50 kg, for example, at least 0.75 kg, for example, at least 1.0 kg, for example, at least 1.25 kg, for example, at least 1.5 kg, for example, at least 1.75 kg, for example, at least 2.0 kg, for example, at least 2.5 kg, for example, at least 3.0 kg, for example, 0.25 to 5.0 kg, for example, 0.25 to 4.0 kg, for example, 0.5 to 4.0 kg.

[0567] 273. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max The method according to one of items 266 to 272, wherein

[0568] 274. A method for treating Charcot-Marie-Tooth disease in a subject resulting in improved manual dexterity, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0569] 275. The method according to item 274, wherein the improvement in manual dexterity can be determined using a 9-hole peg test.

[0570] 276. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max Item 275, the method of claim 275,

[0571] 277. The method of one of items 274 to 276, wherein the subject experiences an improvement in manual dexterity of at least 10%, such as at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%, such as 5% to 95%, for example 5% to 80%, for example 10% to 50%.

[0572] 278. A method for treating Charcot-Marie-Tooth disease in a subject resulting in improved walking ability, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0573] 279. The method according to item 278, wherein the improvement in walking ability is determined using a six-spot step test.

[0574] 280. The method according to item 278, wherein the improvement in walking ability is determined using a 10 meter walk / run test.

[0575] 281. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. maxThe method according to one of items 278 to 280,

[0576] 282. The method according to one of items 278 to 281, wherein the subject experiences an improvement in walking ability of at least 10%, such as at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%, such as 5% to 95%, for example 5% to 80%, for example 10% to 50%.

[0577] 283. The method of one of items 278 to 282, wherein the subject experiences an improvement in walking ability, and the time to complete a 6-spot step test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example at least 0.7 seconds, for example at least 1.0 seconds, such as at least 1.5 seconds, for example at least 2 seconds, for example at least 2.5 seconds, such as at least 3 seconds, for example at least 4 seconds, for example at least 5 seconds, for example between 0.3 seconds and 10 seconds, for example between 0.3 seconds and 5 seconds, for example between 0.5 seconds and 5 seconds.

[0578] 284. The method of one of items 278 to 283, wherein the subject experiences an improvement in walking ability and the time to complete a 10 meter walk / run test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example at least 0.7 seconds, for example at least 1.0 seconds, for example at least 1.5 seconds, such as at least 2 seconds, for example at least 2.5 seconds, for example at least 3 seconds, for example at least 4 seconds, for example at least 5 seconds, such as between 0.3 seconds and 10 seconds, for example between 0.3 seconds and 5 seconds, for example between 0.5 seconds and 5 seconds.

[0579] 285. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in reduced fatigue, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0580] 286. The method according to item 285, wherein the reduction in fatigue is calculated from the distance walked in the first minute to the distance walked in the sixth minute of a 6-minute walk test.

[0581] 287. The method according to one of items 285 to 286, wherein the subject experiences a reduction in fatigue of at least 5%, such as at least 10%, for example at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, for example at least 40%, for example at least 50%, for example at least 60%, for example at least 70%, for example at least 80%, for example between 5% and 95%, for example between 5% and 80%, for example between 10% and 50%.

[0582] 288. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max The method according to one of items 285 to 287,

[0583] 289. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in an increase in a 32-item motor function index score, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0584] 290. The method of item 289, wherein the subject experiences an increase in the motor function index 32-item score of at least 5%, such as at least 10%, for example, at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, for example, at least 40%, for example, at least 50%, for example, at least 60%, for example, at least 70%, for example, at least 80%, for example, 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0585] 291. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 291. The method according to one of items 289 or 290, wherein

[0586] 292. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a decrease in fatigue severity scale score, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0587] 293. The method of item 292, wherein the subject experiences a reduction in the fatigue severity scale score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as at least 15 points, for example, at least 20 points, such as from 0.3 to 30 points, for example, from 0.5 to 20 points, for example, from 0.3 to 10 points.

[0588] 294. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 294. The method according to one of items 292 or 293, wherein

[0589] 295. A method for treating Charcot-Marie-Tooth disease in a subject resulting in improved balance and mobility, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0590] 296. The method of item 295, wherein the improvement in balance and mobility can be determined using a timed "up and go" test.

[0591] 297. The method according to one of items 295 to 296, wherein the subject experiences an improvement in balance and mobility of at least 10%, such as at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%, such as 5% to 95%, for example 5% to 80%, for example 10% to 50%.

[0592] 298. The method of one of items 295 to 296, wherein the subject experiences an improvement in walking ability, and the time to complete a timed "up and go" test is reduced by at least 0.3 seconds, such as at least 0.5 seconds, for example, at least 0.7 seconds, for example, at least 1.0 seconds, for example, at least 1.5 seconds, such as at least 2 seconds, for example, at least 2.5 seconds, for example, at least 3 seconds, for example, at least 4 seconds, for example, at least 5 seconds, such as from 0.3 seconds to 10 seconds, for example, from 0.3 seconds to 5 seconds, for example, from 0.5 seconds to 5 seconds.

[0593] 299. The therapeutically effective dose is a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 299. The method according to one of items 295 to 298,

[0594] 300. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in improved neuromuscular junction transmission, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0595] 301. The method according to item 300, wherein the improvement in the neuromuscular junction is a reduction in jitter and / or blocking, determined using single fiber electromyography.

[0596] 302. The method of one of items 300 or 301, wherein the subject experiences a reduction in jitter of at least 10%, such as at least 15%, for example at least 20%, for example at least 25%, for example at least 30%, such as at least 50%, for example at least 75%, for example at least 100%, for example at least 150%, for example at least 200%, such as between 5% and 95%, for example between 5% and 80%, for example between 10% and 50%.

[0597] 303. The method of one of items 300 or 301, wherein the subject experiences a reduction in jitter of at least 5 μs, such as at least 10 μs, for example at least 15 μs, for example at least 20 μs, for example at least 25 μs, for example at least 30 μs, for example at least 40 μs, for example at least 50 μs, for example at least 75 μs, for example at least 100 μs, for example from 5 μs to 200 μs, for example from 5 μs to 100 μs, for example from 10 μs to 50 μs.

[0598] 304. The method according to one of items 300 or 301, wherein the subject experiences a reduction in blocking of at least 10%, such as at least 15%, for example, at least 20%, for example, at least 25%, for example, at least 30%, such as at least 50%, for example, at least 75%, for example, at least 100%, for example, at least 150%, for example, at least 200%, such as 5% to 95%, for example, 5% to 80%, for example, 10% to 50%.

[0599] 305. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max The method according to one of items 300 to 304,

[0600] 306. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a reduction in overall neuropathy limitation score (ONLS), said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0601] 307. The method of item 306, wherein the subject experiences a reduction in the global neuropathy limitation score after treatment with NMD670, wherein the score is reduced by at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, for example, at least 5 points, such as at least 6 points, for example, at least 8 points, for example, at least 10 points, such as 0.3 to 10 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0602] 308. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 8. The method according to one of items 306 or 307, providing

[0603] 309. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a reduction in CMT Neuropathy Score 2 (CMTNS2) score, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0604] 310. The method of item 309, wherein the subject experiences a reduction in the CMTNS2 score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, such as at least 1 point, for example, at least 2 points, such as at least 3 points, for example, at least 4 points, such as at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as from 0.3 to 20 points, for example, from 0.5 to 6 points, for example, from 0.3 to 5 points.

[0605] 311. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 311. The method according to one of items 309 or 310,

[0606] 312. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a decrease in CMT test score (second version) (CMTES2) score, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0607] 313. The method of item 312, wherein the subject experiences a decrease in the CMTES2 score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as 0.3 to 20 points, for example, 0.5 to 6 points, for example, 0.3 to 5 points.

[0608] 314. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 314. The method according to one of items 312 or 313,

[0609] 315. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a decrease in a CMT Functional Outcome Measure (CMT-FOM) score, the method comprising administering to the subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the therapeutic dose is in the range of 100 mg to 1500 mg.

[0610] 316. The method of item 315, wherein the subject experiences a reduction in the CMT-FOM score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as at least 15 points, for example, at least 20 points, such as from 0.3 to 30 points, for example, from 0.5 to 20 points, for example, from 0.3 to 10 points.

[0611] 317. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 317. The method according to one of items 315 or 316, wherein

[0612] 318. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in an increase in Berg Balance Scale score, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0613] 319. The method of item 318, wherein the subject experiences an increase in the Berg Balance Scale score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, for example, at least 15 points, such as at least 20 points, for example, from 0.3 to 30 points, for example, from 0.5 to 20 points, for example, from 0.3 to 10 points.

[0614] 320. The therapeutically effective dose is a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 310. The method according to one of items 318 or 319, wherein

[0615] 321. A method for treating Charcot-Marie-Tooth disease in a subject, resulting in a decrease in an individualized neuromuscular quality of life score, said method comprising administering to said subject a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutic dose is in the range of 100 mg to 1500 mg.

[0616] 322. The method of item 321, wherein the subject experiences a decrease in the individualized neuromuscular quality of life score of at least 0.3 points, such as at least 0.5 points, for example, at least 0.75 points, for example, at least 1 point, such as at least 2 points, for example, at least 3 points, such as at least 4 points, for example, at least 5 points, for example, at least 6 points, such as at least 8 points, for example, at least 10 points, such as at least 15 points, for example, at least 20 points, such as from 0.3 to 30 points, for example, from 0.5 to 20 points, for example, from 0.3 to 10 points.

[0617] 323. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max 323. The method according to one of items 321 or 322, wherein

[0618] 324. A method for treating a subject suffering from symptoms of Charcot-Marie-Tooth disease, said method comprising administering a therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein said therapeutically effective dose is in the range of 100 mg to 1500 mg.

[0619] 325. A method for the treatment of Charcot-Marie-Tooth disease in a subject having a serum uric acid level greater than 6.5 mg / dL, said method comprising administering to said subject a low dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, until the patient's serum uric acid level decreases to less than 6.5 mg / dL; and then administering to the subject a therapeutic dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, wherein the low dose is in the range of 20 mg to 150 mg, e.g., 25 mg to 100 mg, e.g., 25 mg to 50 mg, and the therapeutic dose is in the range of 200 mg to 1500 mg.

[0620] 326. A method for improving recovery of neuromuscular transmission and / or skeletal muscle function, comprising administering to the subject a composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

[0621] 327. The method according to one of items 256 to 326, wherein the defined period is 21 days.

[0622] 328. The therapeutically effective dose is a dose that produces a C in the range of 2,790 ng / mL to 76,700 ng / mL in the subject. max The method according to one of items 256 to 327,

[0623] 329. The therapeutically effective dose is a dose that produces an AUC in the range of 16,700 ng / mL to 534,000 ng / mL in the subject. inf The method according to one of items 256 to 328, wherein

[0624] 330. The therapeutically effective dose of the compound is a T max The method according to one of items 256 to 329, comprising:

[0625] 331. The therapeutically effective dose of the compound is a T max The method according to one of items 256 to 329, comprising:

[0626] 332. The method according to one of items 256 to 331, wherein the therapeutically effective dose is in the range of 100 mg to 600 mg.

[0627] 333. The method according to one of items 256 to 331, wherein the therapeutically effective dose is in the range of 200 mg to 600 mg.

[0628] 334. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 100 mg.

[0629] 335. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 150 mg.

[0630] 336. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 200 mg.

[0631] 337. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 250 mg.

[0632] 338. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 300 mg.

[0633] 339. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 350 mg.

[0634] 340. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 400 mg.

[0635] 341. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 500 mg.

[0636] 342. The method according to one of items 256 to 331, wherein the therapeutically effective dose is 600 mg.

[0637] 343. The method according to one of items 256 to 342, wherein the therapeutically effective dose is administered once, twice, three or four times daily.

[0638] 344. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0639] 345. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0640] 346. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0641] 347. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 100 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0642] 348. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0643] 349. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0644] 350. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0645] 351. The method according to one of items 256 to 326, wherein the therapeutically effective dose is 200 to 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0646] 352. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0647] 353. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0648] 354. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0649] 355. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 100 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0650] 356. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0651] 357. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0652] 358. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0653] 359. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 150 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0654] 360. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0655] 361. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0656] 362. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0657] 363. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 200 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0658] 364. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0659] 365. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0660] 366. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0661] 367. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 250 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0662] 368. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0663] 369. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0664] 370. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0665] 371. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 300 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0666] 372. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0667] 373. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0668] 374. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0669] 375. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 350 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0670] 376. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered once a day.

[0671] 377. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0672] 378. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0673] 379. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered four times a day.

[0674] 380. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0675] 381. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0676] 382. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered twice a day.

[0677] 383. The method according to one of items 256 to 326, wherein the therapeutically effective dose is about 600 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, and the composition is administered three times a day.

[0678] 384. The method according to one of items 256 to 383, wherein the therapeutically effective dose is administered orally to the subject.

[0679] 385. The composition for use or method of any one of the preceding items, wherein the method further comprises administering to the subject a second therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, either 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or at least 7 days after the first therapeutically effective dose is administered.

[0680] 386. The composition or method for use according to item 385, wherein the second therapeutically effective dose is 100 mg to about 1500 mg.

[0681] 387. The composition or method for use according to item 385, wherein the second therapeutically effective dose is the same as the first therapeutically effective dose administered to the subject.

[0682] 388. The composition or method for use of any one of items 385 to 387, wherein the method further comprises administering to the subject a third therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, any of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or at least 7 days after the therapeutically effective dose is administered.

[0683] 389. The composition or method for use according to item 388, wherein the third therapeutically effective dose is 100 mg to about 1500 mg.

[0684] 390. The composition or method for use according to item 388, wherein the third therapeutically effective dose is the same as the first therapeutically effective dose and / or the second therapeutically effective dose administered to the subject.

[0685] 391. The composition or method for use of any one of the preceding items, wherein said administration of said therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is repeated at least 1, 2, 3, 4, 5, or 6 times weekly.

[0686] 392. The composition or method for use of any one of the preceding items, wherein said administration of said therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is repeated at least 1 to 3 times weekly, 2 to 5 times weekly, or 3 to 6 times weekly.

[0687] 393. The composition or method for use of any one of the preceding items, wherein said administration of said therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is repeated daily.

[0688] 394. The composition or method for use of any one of the preceding items, wherein said administration of said therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is repeated 1, 2, 3, 4, 5, 6, 7, or 8 times daily.

[0689] 395. The composition or method for use of any one of the preceding items, wherein the administration of the therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is repeated 1 to 8 times per day or 2 to 5 times per day.

[0690] 396. The composition or method for use of any one of the preceding items, wherein the therapeutically effective dose of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is administered at least once daily.

[0691] 397. The composition or method for us...

Claims

1. 1. A composition comprising (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, for use in a method for treating Charcot-Marie-Tooth disease in a subject, wherein the composition is for administration at a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

2. The composition for use according to claim 1, wherein the therapeutic dose is 200 to 600 mg.

3. 10. A composition for use according to any one of the preceding claims, wherein the therapeutic dose is administered once, twice or three times daily.

4. 10. The composition for use according to any one of the preceding claims, wherein the composition is administered orally.

5. 10. A composition for use according to any one of the preceding claims, wherein the composition is in solid dosage form.

6. 7. The composition for use according to claim 6, wherein the composition comprises silicified microcrystalline cellulose.

7. 10. The composition for use according to any one of the preceding claims, wherein the subject is afflicted with CMT1, CMT2, CMT3 or CMT4.

8. The composition is administered orally using a solid dosage form and provides a plasma concentration-time profile of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, having a mean C ｍａｘ 12,760 to 27,440 ng / mL after administration of a single dose of 400 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

9. 10. The composition for use according to any one of the preceding claims, wherein the subject experiences an increase in total distance walked as determined using a 6-minute walk test after treatment with (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

10. (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, and Peripheral myelin protein 22 (PMP22) downregulator A kit of parts or composition comprising:

11. 11. The kit of parts of claim 10, wherein the kit of parts comprises 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof.

12. 12. A kit of parts according to any one of claims 10 or 11 for use in the treatment of Charcot-Marie-Tooth disease.

13. 12. The kit of parts according to claim 10 or 11 for use in a method of treatment for the treatment of Charcot-Marie-Tooth disease, wherein the kit of parts is for administration of a therapeutic dose of 100 to 1500 mg of (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid.

14. 14. The kit of parts for use according to any one of claims 12 or 13, wherein the therapeutic dose of the (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid, or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, is 200 to 600 mg.

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