Compositions and methods for treating muscle atrophy

Abstract

Disclosed are compositions and methods for the treatment of skeletal muscle atrophy. In particular, the disclosure features a method of treating skeletal muscle atrophy with a composition comprising glyoxylate or pharmaceutically equivalent salts thereof in an individual. Additional methods and compositions for treating, mitigating, or preventing skeletal muscle atrophy are provided.

Description

[0001]PATENT ATTORNEY DOCKET NO.: 01948-291WO2 COMPOSITIONS AND METHODS FOR TREATING MUSCLE ATROPHY TECHNICAL FIELD This disclosure relates to the field of skeletal muscle atrophy. BACKGROUND Forty-two percent of older adults have one or more physical limitations in part due to age-related wasting, weakness, and diminished quality of muscles, which are referred to as sarcopenia. Sarcopenia is closely associated with increased risk of falls and other injuries leading to loss of independence and increased mortality. Moreover, declining muscle health increases the risk of type 2 diabetes, hyperlipidemia, and obesity, and diminished muscle health is associated with neurodegeneration. For these reasons, maintaining healthy and robust skeletal muscle should be an important part of standard preventive care for all older adults. Beyond exercise programs that yield limited long-term compliance, there are no widely used approaches to treat acquired or non-genetic forms of skeletal muscle atrophy, such as sarcopenia. Thus, there remains a need in the field for treatment interventions for skeletal muscle atrophy disorders, such as sarcopenia. SUMMARY OF THE INVENTION In one aspect, the disclosure features a method of treating progressive skeletal muscle atrophy in a subject in need thereof by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject. In a further aspect, the disclosure features a method of treating cognitive decline in a subject exhibiting progressive skeletal muscle atrophy by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject. In a further aspect, the disclosure features a method of treating excess adiposity or obesity in a subject exhibiting progressive skeletal muscle atrophy by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject. In some embodiments, the progressive skeletal muscle atrophy is due to an age-related condition. In some embodiments, the progressive skeletal muscle atrophy is due to cachexia. In some embodiments, the progressive skeletal muscle atrophy is due to sarcopenia. In some embodiments, the progressive skeletal muscle atrophy is due to amyotrophic lateral sclerosis (ALS). In some embodiments, the progressive skeletal muscle atrophy is due to a muscular dystrophy (e.g., Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, myotonic muscular dystrophy, Limb-Girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, distal muscular dystrophy, or oculopharyngeal muscular dystrophy) or a congenital myopathy (e.g., a core myopathy, a centronuclear myopathy, or a nemaline myopathy). In some embodiments, the progressive skeletal muscle atrophy is due to an underlying immunological or inflammatory illness, a neurodegenerative disease, cellular or mitochondrial dysfunction, a genetic mutation, malnutrition, or diminished physical activity. In some embodiments, the progressive skeletal muscle atrophy is due to idiopathic skeletal muscle atrophy. In another aspect, the disclosure features a method of treating a subject exhibiting progressive PATENT ATTORNEY DOCKET NO.: 01948-291WO2 skeletal muscle atrophy by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject. In some embodiments, the progressive skeletal muscle atrophy is due to an age-related condition. In some embodiments, the progressive skeletal muscle atrophy is due to cachexia. In some embodiments, the progressive skeletal muscle atrophy is due to sarcopenia. In some embodiments, the progressive skeletal muscle atrophy is due to amyotrophic lateral sclerosis (ALS). In some embodiments, the progressive skeletal muscle atrophy is due to a muscular dystrophy (e.g., Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, myotonic muscular dystrophy, Limb-Girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, Emery- Dreifuss muscular dystrophy, distal muscular dystrophy, or oculopharyngeal muscular dystrophy) or a congenital myopathy (e.g., a core myopathy, a centronuclear myopathy, or a nemaline myopathy). In some embodiments, the progressive skeletal muscle atrophy is due to an underlying immunological or inflammatory illness, a neurodegenerative disease, cellular or mitochondrial dysfunction, a genetic mutation, malnutrition, or diminished physical activity. In some embodiments, the progressive skeletal muscle atrophy is due to idiopathic skeletal muscle atrophy. In another aspect, the disclosure features a method of treating amyotrophic lateral sclerosis (ALS), a muscular dystrophy (e.g., Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, myotonic muscular dystrophy, Limb-Girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, distal muscular dystrophy, or oculopharyngeal muscular dystrophy), or a congenital myopathy (e.g., a core myopathy, a centronuclear myopathy, or a nemaline myopathy) by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject. In an embodiments of all aspects of the disclosure, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the human is younger than 18 years old (e.g., 17 years old, 16 years old, 15 years old, 14 years old, 13 years old, 12 years old, 11 years old, 10 years old, 9 years old, 8 years old, 7 years old, 6 years old, 5 years old, 4 years old, 3 years old, 2 years old, 1 year old, or younger than 1 year old). In some embodiments, the human is 18 years old or older (e.g., 18 years old, 19 years old, 20 years old, 21 years old, 22 years old, 23 years old, 24 years old, 25 years old, 30 years old, 35 years old, 40 years old, 45 years old, 50 years old, or older). In some embodiments, the human is above the age of 40 years old. In some embodiments, the human is between the ages of 70 and 85 years old (e.g., 70 years old, 71 years old, 72 years old, 73 years old, 74 years old, 75 years old, 76 years old, 77 years old, 78 years old, 79 years old, 80 years old, 81 years old, 82 years old, 83 years old, 84 years old, or 85 years old). In some embodiments, the human is above the age of 85 years old (e.g., 86 years old, 87 years old, 88 years old, 89 years old, 90 years old, 91 years old, 92 years old, 93 years old, 94 years old, 95 years old, or older). In some embodiments of all aspects of the disclosure, the subject exhibits or is at risk of loss of skeletal muscle mass or function prior to administration of the composition. In some embodiments of all aspects of the disclosure, the skeletal muscle mass of the subject is or has been determined by performing electrical impedance myography (EIM), magnetic resonance imaging (MRI), and / or dual-energy X-ray absorptiometry (DXA). In some embodiments, the skeletal muscle function of the subject is or has been determined by performing EIM, a strength assessment of the subject, and / or a mobility assessment of the subject. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 In some embodiments of all aspects of the disclosure, the subject is characterized as having sarcopenia based on at least one criterion from a strength or mobility assessment summarized in Table 1. In some embodiments of all aspects of the disclosure, after administration of the composition, the method further includes monitoring the subject for changes in skeletal muscle mass of the subject relative to an assessment of the subject’s skeletal muscle mass prior to administration of the composition. In some embodiments of all aspects of the disclosure, the composition is administered at a dose between 1 mg / kg and 10 mg / kg (e.g., 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg). In some embodiments, the composition is administered at a dose between 35 mg and 900 mg (e.g., 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, or 900 mg). In some embodiments of all aspects of the disclosure, the dose of the composition is administered one or more times weekly (e.g., one, two, three, four, or more). In some embodiments, the dose of the composition is administered daily. In some embodiments of all aspects of the disclosure, the method includes administering one or more additional therapies. In some embodiments, the additional therapy includes an exercise program and / or a dietary program such as a high-leucine diet or a high-protein diet. In some embodiments, the additional therapy includes administration of β-aminoisobutyric acid, a stereoisomer, or a pharmaceutically acceptable salt form thereof. In some embodiments, the additional therapy includes administration of a sirtuin-1 (SIRT1) activator, optionally a cyclobutene or a cyclobutene-scaffold-based molecule. In some embodiments, the additional therapy includes administration of an inhibitory nucleic acid that targets C9ORF72, SOD1, TARDBP, FUS, PFN1, NEFH, PRPH, or DCTN1. In some embodiments, the additional therapy includes administration of edaravone, dextromethorphan hydrobromide and quinidine sulfate, riluzole, or tofersen. In some embodiments of all aspects of the disclosure, the composition is administered as a single dose. In some embodiments, the composition is administered as two or more separate doses (e.g., two, three, four or more). In some embodiments, the composition is administered one or more times per day, week, month, or year (e.g., 1 to 3 times, 1 to 5 times, or 1 to 10 times). In some embodiments of all aspects of the disclosure, the composition is administered to the subject by oral, intravenous, cutaneous, subcutaneous, intradermal, nasal, pulmonary, intramuscular, or intraperitoneal administration. In some embodiments, the composition is administered subcutaneously. In some embodiments, the composition is administered by intramuscular injection. In some embodiments, the composition is administered by oral administration. In some embodiments of all aspects of the disclosure, the composition is administered at a volume between 350 μL and 3.5 mL (e.g., 350 μL, 375 μL, 400 μL, 425 μL, 450 μL, 475 μL, 500 μL, 525 μL, 550 μL, 575 μL, 600 μL, 625 μL, 650 μL, 625 μL, 650 μL, 675 μL, 700 μL, 725 μL, 750 μL, 775 μL, 800 μL, 825 μL, 850 μL, 875 μL, 900 μL, 925 μL, 950 μL, 975 μL, 1 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2 mL, 2.25 mL, 2.5 mL, 2.75 mL, 3 mL, 3.25 mL, or 3.5 mL). In some embodiments of all aspects of the disclosure, the composition has a sustained release formulation. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 In some embodiments of all aspects of the disclosure, after administration of the composition, the subject is characterized as exhibiting an increase in skeletal muscle mass relative to the subject prior to administration of the composition or relative a control subject. In some embodiments of all aspects of the disclosure, the increase in skeletal muscle mass is at least a 10% increase (e.g., 10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, or more). In some embodiments, the increase in skeletal muscle mass is between a 15% and 20% increase (e.g., 15%, 16%, 17%, 18%, 19%, or 20%). In some embodiments, of all aspects of the disclosure after administration of the composition, the subject is characterized as exhibiting an increase in skeletal muscle function relative to the subject prior to administration of the composition or relative a control subject. In some embodiments, the increase in skeletal muscle function is at least a 15% increase (e.g., an increase of 20% or 25% in skeletal muscle function, as compared to skeletal muscle function in a control subject or in a subject not administered the composition). In some embodiments of all aspects of the disclosure, the monitoring includes performing EIM, strength assessment, and / or mobility assessment. In some embodiments of all aspects of the disclosure, the method further includes changing the dose amount, frequency of administration, or term of administration of the composition based on a result of the monitoring. In some embodiments, the change includes an increase in the dose amount, frequency of administration, and / or term of administration of the composition. In some embodiments, the dose is increased by at least 50% relative to a prior dose administered to the subject (e.g., 50%, 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or more than 100%). In some embodiments, the frequency of administration is increased by at least one additional time of administration per day, week, month, or year (e.g., 1 to 3 times, 1 to 5 times, or 1 to 10 times). In some embodiments of all aspects of the disclosure, the method further includes monitoring the skeletal muscle mass or skeletal muscle function of the subject after the change. In some embodiments, the monitoring includes performing EIM, a strength assessment, and / or a mobility assessment. In some embodiments, the method further includes measuring a level of a metabolite in a blood sample obtained from the subject. In some embodiments, the blood sample is whole blood, plasma, and / or serum. In some embodiments, the metabolite is a cofactor or byproduct of the citric acid cycle. In some embodiments, the level of the metabolite is measured prior to administration of the composition. In some embodiments, the level of the metabolite is measured one or more times during the course of a treatment regimen comprising administration of the composition. In some embodiments, the level of the metabolite indicates changes in skeletal muscle of the subject. In some embodiments, the metabolite is selected from the group consisting of a lipid, a carbohydrate, a glycan, a citric acid cycle intermediate, a bile acid, an amino acid, an organic acid, a purine, and a pyrimidine. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 In some embodiments, the metabolite is a reduced or oxidized form of nicotinamide adenine dinucleotide (NAD). In some embodiments of all aspects of the disclosure, glyoxylate or a pharmaceutically acceptable salt thereof is supplemented or substituted with a composition including any one or more of a structurally similar compound selected from glyceraldehyde, glyoxal, pyruvate, oxaloacetate, methylglyoxal, alpha-ketobutyrate, alpha-ketoglutarate, 3-methyl-2-oxovaleric acid, dihydroxyacetone, acetaldehyde, oxalate, glycolate, malate, lactate, or a combination thereof and a pharmaceutically acceptable excipient. Definitions Unless otherwise defined herein, scientific and technical terms used herein have the meaning that is commonly understood by those of ordinary skill in the art. In the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The use of "or" means "and / or" unless stated otherwise. The use of the term "including," as well as other forms, such as "includes" and "included," is not limiting. As used herein, the term "about," as applied to one or more values of interest, refers to a value that falls within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of a stated reference value, unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). As used herein, the terms “prevent” or “preventing” refers to precluding, averting, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit, or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. “Prevention” includes reduction of risk and / or severity of a condition or disorder. As used herein, the terms “treatment” or " treat” refers to prophylactic or preventive treatment that prevents and / or slows the development of a pathologic condition or disorder. “Treatment” or “treat” may also refer to curative interventions and therapeutic measures intended to improve or reverse, reduce the severity, or ameliorate any one or more manifestations of a particular pathologic disease or disorder. The terms do not necessarily imply that a subject is treated until total recovery. As used herein, the term “diagnosed” means having been subjected to a physical examination by a skilled practitioner, for example, a physician, or subjected to an assay, such as a biological or chemical assay (including, e.g., a bioimpedance assay, such as electrical impedance myography (EIM)), and found to have a condition that can be treated by a compound, composition, or method disclosed herein. For example, “diagnosed with a muscle atrophy disorder” means having been subjected to a physical examination by said skilled practitioner or subjected to a diagnostic assay and found to have a condition that can be treated by a method that includes administration of a compound (e.g., glyoxylate or an analog thereof) or composition containing the compound that can promote muscle health, promote normal muscle function, and / or promote healthy aging muscles. As used herein, the terms “administering” or “administration” refer to a method of providing a pharmaceutical preparation, such as a pharmaceutical composition described herein, to a subject. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Administration methods are well known in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. A preparation can also be administered prophylactically; that is, administered for prevention of a disease or a condition or one or more symptoms thereof. As used herein, the term “pharmaceutically acceptable” describes material that is not biologically or otherwise undesirable, e.g., without causing an unacceptable level of undesirable biological effects or interacting in a deleterious manner. As used herein, the term “pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions suspensions, or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, among others), carboxymethyl cellulose and suitable mixtures thereof, and injectable organic esters such as ethyl oleate. Suitable inert carriers may include sugars such as lactose. As used herein, the term “dose” refers to the amount of a pharmaceutical composition, such as a pharmaceutical composition described herein, administered to a subject. As used herein, the term “dosage form” refers to a physically discrete unit suitable as a unitary dosage, such as a pill, tablet, caplet, hard capsule or soft capsule, each unit containing a predetermined quantity of a drug (e.g., glyoxylate or an analog thereof or other agent disclosed herein). As used herein, the terms “duration of treatment” or “course of treatment” refers to the length of time that a subject receives treatment for muscle atrophy. The duration of treatment may be determined based on muscle condition or instances of muscle improvement (e.g., improved muscle mass, improved muscle function, improved mobility, improved strength, or a combination thereof), or the duration of treatment may be recommended indefinitely or continuously, e.g., as may be determined by a medical practitioner or healthcare provider. As used herein, the terms “time-release formulation” and “sustained release formulation” refer to a pharmaceutical composition that is formulated to release the prepared medication over an extended period of time such that there is a time lag prior to the release of the composition, or the dosage form releases the composition at a predetermined rate. A time-release formulation may be utilized to improve the pharmacokinetics, pharmacodynamics, and / or the biodistribution of a composition in a subject, such as a composition described herein. As used herein, the term “salt” refers to any pharmaceutically acceptable salt, such as a non-toxic acid addition salt, metal salt, or metal complex, commonly used in the pharmaceutical industry. Acid addition salts include organic acids, such as acetic, lactic, palmoic, maleic, citric, cholic acid, capric acid, caprylic acid, lauric acid, glutaric, glucuronic, glyceric, glycocolic, glyoxylic, isocitric, isovaleric, lactic, malic, oxalo acetic, oxalosuccinic, propionic, pyruvic, ascorbic, succinic, benzoic, palmitic, suberic, salicylic, tartaric, methanesulfonic, toluenesulfonic, and trifluoroacetic acids, and inorganic acids, such as PATENT ATTORNEY DOCKET NO.: 01948-291WO2 hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium, among others. As used herein, the term “muscle atrophy” refers to a condition in which a subject may exhibit a loss of muscle mass or loss of muscle function due to wasting or loss of muscle tissue. Muscle atrophy may occur secondary to an underlying genetic disease or acquired condition, such as a neurodegenerative disorder (e.g., amyotrophic laterel sclerosis), a cancer, an autoimmune or immune disorder, an inflammatory condition, an infection, or other such condition. Muscle atrophy may occur due to advanced age, malnutrition or nutrient deficiencies, or diminished physical activity. Muscle atrophy may be determined by a skilled practitioner, such as a physician, using methods known in the art and methods described herein, including a diagnostic assay (e.g., a biological or chemical assay, including a bioimpedance assay, such as electrical impedance myography (EIM)). As used herein, the term “sarcopenia” refers to a multi-factorial condition that results in a loss of skeletal muscle mass and decline in muscle strength and muscle function due to advancing age. Sarcopenia is associated with physical frailty and accumulation of adipose tissue, as well as other pathophysiological changes, such as impaired neuro-muscular transition, altered excitation and contraction coupling, impaired regenerative capacity linked to stem cell exhaustion, and defects of mitochondria and energy metabolism in myofibers. Sarcopenia is often diagnosed by a medical practitioner using methods known in the art and described herein. As used herein, the term “cachexia” refers to a condition that results in a loss of skeletal muscle mass and / or body weight that is typically secondary to an underlying acute or chronic disease including but not limited to a neurodegenerative disorder (e.g., amyotrophic lateral sclerosis), a cancer, an autoimmune or immune disorder, an inflammatory condition, or an infection. Cachexia is often diagnosed when a subject has a weight loss of more than 5% body mass or when weight loss is more than 2% body mass if the subject has a body-mass index of less than 20 kg / m. As used herein, the term “amyotrophic lateral sclerosis (ALS)” refers to a progressive condition that results in the degeneration of motor neurons in the brain and spinal cord. As ALS progresses, motor neurons fail to transmit signals to skeletal muscles, leading to skeletal muscle weakening and atrophy. The most common type of ALS is sporadic ALS, in which the onset of the disease occurs with no clear associated risk factors or family history. Familial ALS, which accounts for approximately 10% of diagnosed ALS cases, is a genetic form of the disease and may be caused by underlying mutations in identified genes associated with ALS, including chromosome 9 open reading frame 72 (C9ORF72), superoxide dismutase 1 (SOD1), TAR DNA binding protein (TARDBP), FUS RNA binding protein (FUS), profilin-1 (PFN1), neurofilament heavy chain (NEFH), peripherin (PRPH), and dynactin subunit I (DCTN1). Thus, an individual that has one or more mutations in one or more of these genes may be identified as an individual at risk of developing ALS. Additional genes that are associated with ALS have been described elsewhere, e.g., Volk, et al. (Med Genet.30(2):252-258, 2018), which is hereby incorporated by reference. An individual that has a family history of ALS may be identified as an individual at risk of developing ALS. Additional risk factors of ALS include brain and spinal cord injuries, smoking, and exposure to environmental toxins (e.g., pesticides, insecticides, herbicides, cyanide, vinyl chloride, benzene, or formaldehyde) and / or heavy metals (e.g., lead, zinc, copper, mercury, or manganese). ALS may be diagnosed by a medical professional using diagnostic methods known in the art, such as PATENT ATTORNEY DOCKET NO.: 01948-291WO2 magnetic resonance imaging (MRI) and / or electromyography (EMG), which includes a nerve conduction study and / or a needle exam, which are methods for measuring the electrical activity of nerves and muscle fibers. As used herein, the terms “myofibers” or “muscle fibers” refer to the elongated contractile fibers that compose skeletal muscle tissue. Myofibers are single, multinucleated cells and are broadly classified as either slow- or fast-twitch type based on their energetics and oxidative metabolism. As used herein, the term “electrical impedance myography (EIM)” refers to a non-invasive technique to measure muscle composition (e.g., muscle mass and / or muscle quality) in a subject, in which a weak, multi-frequency electrical current is forced through a localized area of tissue and the consequent voltage patterns are measured. The relationship between the applied current and the measured voltage provides spectroscopic impedance, which is a complex value that includes the resistance, which is sensitive to both intra- and extra-cellular properties of the tissues, and the reactance, which is sensitive to cell membrane properties and cell size. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings are included to illustrate embodiments of the disclosure and further an understanding of its implementations. FIG.1 is a schematic showing glyoxylate metabolism and how the molecule generates both NADH and NAD+ cofactors in the cytosol and the mitochondria of a cell. FIG.2 is a schematic showing the citric acid cycle and its various components for the production of carbohydrates, amino acids, and fatty acids. FIG.3 is a schematic showing the role of glyoxylate and its conversion to other components in the citric acid cycle via coenzymes. FIG.4 is an image showing an overview of the mechanistic pathways differentially targeted by glyoxylate, β-aminoisobutyric acid (BAIBA), and cyclobutane-scaffold-based molecules. FIG.5 is a graph showing the inhibition of drug-induced atrophy mediated by SIRT1 activator analogs. The diameter of myotubes in a myoblast C2C12 cell line were measured following exposure to a vehicle control, 100ng / mL dexamethasone (Dexa), or dexamethasone plus 5 μM of one of three analogs of the SIRT1 activator (CB1, CB2, or CB3). Data were blinded for collection and analyses. Asterisk (*) indicates p<0.05. FIG.6A is an image depicting the musculature and muscle anatomy of zebrafish. The left image shows a hematoxylin and eosin (H&E)-stained cross-section of zebrafish trunk muscles. The right image is a schematic labelling the anatomical features of the tissue shown on the left. FIG.6B are representative images showing H&E-stained cross-sections of myofibers from young zebrafish. Young zebrafish exhibit large polygonal-shaped myofibers sheathed in a layer of ordered connective tissue. Scale bar is 50 μm. FIG.6C are representative images showing H&E-stained cross-sections of myofibers from aged zebrafish. Aged zebrafish exhibit smaller myofibers with disordered connective tissue and increased extracellular space. Scale bar is 50 μm. FIG.6D is a graph showing the representative distribution of cross-sectional fiber area of muscle tissue from young and aged zebrafish. From 1304 ± 128 μm2in young animals versus 676 ± 383 μm2in old animals (p=0.004, FDR≤0.05). PATENT ATTORNEY DOCKET NO.: 01948-291WO2 FIG.7A is a schematic showing a method of measuring swimming performance in zebrafish. FIG.7B is an image showing representative tracking of swimming performance of young zebrafish captured via high-speed digital videos. FIG.7C is an image showing representative tracking of swimming performance of aged zebrafish captured via high-speed digital videos. FIG.7D is an image showing the exemplary movement that defines the turn angle in swimming performance assessments. FIG.7E is a graph showing the distribution of the turn angles in young and aged zebrafish. Young zebrafish were capable of body maneuvers that resulted in deeper turn angles as compared to aged fish (16.9 ± 3.5 degrees versus 9.7 ± 2.7 degrees, p=0.0003, FDR≤0.05). FIG.7F is a graph showing the Spearman correlation between a measured turn angle in zebrafish and measured myofiber cross-sectional area (CSA). FIG.7G is an image showing the exemplary movement and variables that define the angular velocity determined in swimming performance assessments. FIG.7H shows the distribution of angular velocity in young and aged zebrafish. Young fish exhibited greater angular velocity as compared to aged fish, indicating that it takes more time for aged fish to change their direction of travel (163.5 ± 35.0 versus 72.4 ± 30.7 degrees / s, p=0.0003, FDR≤0.05). FIG.7I is an image showing the Spearman correlation between a measured angular velocity in zebrafish and measured myofiber CSA. FIG.7J is an image showing the exemplary movement that defines the lateral body motion determined in swimming performance assessments. FIG.7K is a graph showing the distribution of lateral body motion in young and aged zebrafish. FIG.7L is a graph showing the Spearman correlation between a measured lateral motion in zebrafish and measured myofiber CSA. FIG.8A is a schematic showing an image of H&E-stained zebrafish skin and a diagram of an electrode measuring zebrafish skeletal muscle for surface EIM measurements and analyses. FIG.8B is an image showing a diagram of the customized set-up built to conduct surface EIM experiments with zebrafish. As shown in the diagram insert, a 3 mm probe comprising needle electrodes is placed on the fish’s skin to collect impedance data. FIG.8C is an image showing the basic concepts of impedance measurements in healthy and sarcopenic muscle. Compositional and structural features of bulk muscle tissue affect its electrical conduction properties or the muscle’s ability to resist or conduct electric current and store electric charge. FIG.9A is a graph of the measured phase over multiple frequencies from EIM measurements of muscle tissue in young and aged zebrafish. FIG.9B is a graph of the measured reactance over multiple frequencies from EIM measurements of muscle tissue in young and aged zebrafish. FIG.9C is a graph of the measured resistance over multiple frequencies from EIM measurements of muscle tissue in young and aged zebrafish. FIG.9D is a single frequency 2 kHz graph showing phase differences between young and aged zebrafish muscle tissue as measured by EIM. **** indicates p<0.0001. FIG.9E is a single frequency 2 kHz graph showing reactance differences between young and PATENT ATTORNEY DOCKET NO.: 01948-291WO2 aged zebrafish muscle tissue as measured by EIM. **** indicates p<0.0001. FIG.9F is a single frequency 2 kHz graph showing resistance differences between young and aged zebrafish muscle tissue as measured by EIM. *** indicates p<0.001. FIG.9G is a graph showing the Spearman correlation between the 2 kHz phase data and myofiber CSA measurements. FIG.9H is a graph showing the Spearman correlation between the 2 kHz reactance data and myofiber CSA measurements. FIG.9I is a graph showing the Spearman correlation between the 2 kHz resistance data and myofiber CSA measurements. FIG.10A is a graph showing the multifrequency phase measurements of muscle tissue from young zebrafish, aged zebrafish, and aged zebrafish treated with 80 μM glyoxylate, as determined by EIM. FIG.10B is a graph showing the multifrequency reactance measurements of muscle tissue from young zebrafish, aged zebrafish, and aged zebrafish treated with 80 μM glyoxylate, as determined by EIM. FIG.10C is a graph showing the multifrequency resistance measurements of muscle tissue from young zebrafish, aged zebrafish, and aged zebrafish treated with 80 μM glyoxylate, as determined by EIM. FIG.10D is a graph showing improved single 2 kHz frequency phase measurements of muscle tissue of aged zebrafish treated with 80 μM glyoxylate compared to aged zebrafish with no treatment. The graph shows phase data of single frequency 2 kHz EIM measurements of young fish, aged fish, and aged fish treated with either 10 μM or 80 μM glyoxylate as indicated. **** indicates p<0.0001. FIG.10E is a graph showing improved single 2 kHz frequency reactance measurements of muscle tissue of aged zebrafish treated with 80 μM glyoxylate compared to aged zebrafish with no treatment. The graph shows reactance data of single frequency 2 kHz EIM measurements of young fish, aged fish, and aged fish treated with either 10 μM or 80 μM glyoxylate as indicated. **** indicates p<0.0001. FIG.10F is a graph showing improved single 2 kHz frequency resistance measurements of muscle tissue of aged zebrafish treated with 80 μM glyoxylate compared to aged zebrafish with no treatment. The graph shows resistance data of single frequency 2 kHz EIM measurements of young fish, aged fish, and aged fish treated with either 10 μM or 80 μM glyoxylate as indicated. **** indicates p<0.0001. FIG.11A is a graph showing a dose-dependent increase of myofiber CSA in aged muscle tissue treated with 10 µM or 80 µM glyoxylate, where * p<0.05 and **** p<0.0001. FIG.11B is an image showing representative images of H&E-stained cross-sections of myofibers from young zebrafish, aged zebrafish, aged zebrafish treated with 10 µM glyoxylate, and aged zebrafish treated with 80 µM glyoxylate. FIG.12 is an image showing a Western blot for human and zebrafish SOD1 protein in adult skeletal muscle tissue and a schematic diagram (above) for ubiquitous overexpression of mutant SOD1 protein (i.e., SODG93A) in zebrafish, which is controlled by a CMV reporter and includes a green fluorescent protein reporter. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 FIG.13 is a schematic diagram showing a timeline of phenotypic changes that occur in the SODG93AALS zebrafish model, in which early pathophysiological changes in the nervous system begin to develop at the neuromuscular junction at about 20 weeks of age. The disease progresses between 30-60 weeks of age, with loss of motor neurons and skeletal muscle atrophy being observed at 40 weeks of age. This gradual and incremental degeneration of the neuromuscular system is characteristic of human ALS. FIG.14A is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue sections from wildtype zebrafish at the 40-week time point. The central canal is shown by an arrow. Scale bar is 50 µm. FIG.14B is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue sections from SODG93Azebrafish at the 40-week time point. The central canal is shown by an arrow. The scale is the same as FIG.14A. FIG.14C is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue sections from wildtype zebrafish at the 40-week time point. The central canal, motor neurons, and glial cells are shown by an arrow. Scale bar is 50 µm. FIG.14D is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue sections from SODG93Azebrafish at the 40-week time point. The central canal, motor neurons, and glial cells are shown by an arrow. The scale is the same as FIG.14C. FIG.15 is a graph depicting the number of motor neurons counted in wildtype and SODG93Azebrafish at the 20-week and 40-week time points. FIG.16A is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue of wildtype zebrafish at the 20-week time point. Scale bar is 25 µm. FIG.16B is a representative brightfield micrograph of Cresyl violet-stained spinal cord tissue of SODG93Azebrafish at the 20-week time point. Scale bar is 25 µm. FIG.17A is a representative photograph of wildtype and SODG93Azebrafish at 20 weeks of age and schematic diagrams indicating the location of the trunk thickness measurements. FIG.17B is a representative photograph of wildtype and SODG93Azebrafish at 40 weeks of age and schematic diagrams indicating the location of the trunk thickness measurements. FIG.17C is a graph depicting the measured weight of wildtype and SODG93Azebrafish at 20 or and 40 weeks of age. **** indicates p<0.0001. FIG.17D is a graph depicting the measured trunk thickness of wildtype and SODG93Azebrafish at 20 or and 40 weeks of age. **** indicates p<0.0001. FIG.18A is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 20 weeks of age. Scale bar is 100 µm. FIG.18B is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SODG93Azebrafish at 20 weeks of age. FIG.18C is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 20 weeks of age. Scale bar is 50 µm. FIG.18D is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SODG93Azebrafish at 20 weeks of age. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 FIG.18E is a graph showing the mean CSA of myofibers of the epaxial caudal musculature in SOD1G93Aand wildtype zebrafish FIG.19A is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 40 weeks of age. FIG.19B is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SODG93Azebrafish at 40 weeks of age. Scale bar is 100 µm. FIG.19C is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 40 weeks of age. FIG.19D is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SODG93Azebrafish at 40 weeks of age. Scale bar is 50 µm. FIG.20A is a graph showing the measured CSA of type 2 myofibers of wildtype and SODG93Azebrafish at 40 weeks of age. FIG.20B is a graph showing the relative distribution of cross-sectional type 2 myofiber area in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.21A is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 40 weeks of age. Scale bar is 500 µm. FIG.21B is a schematic diagram depicting anatomical features of the trunk musculature of zebrafish, in which the spinal cord, type 1 myofibers, and type 2 myofibers are indicated. FIG.21C is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of wildtype zebrafish at 40 weeks of age. FIG.21D is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SOD1G93Azebrafish at 40 weeks of age. Scale bar is 50 µm. FIG.22A is a graph showing the measured CSA of type 1 myofibers of wildtype and SODG93Azebrafish at 40 weeks of age. FIG.22B is a graph showing the relative distribution of cross-sectional type 1 myofiber area in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.23A a graph of the measured phase over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 20 weeks of age. FIG.23B is a graph of the measured reactance over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 20 weeks of age. FIG.23C is a graph of the measured resistance over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 20 weeks of age. FIG.23D a graph of the measured phase over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.23E is a graph of the measured reactance over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.23F is a graph of the measured resistance over multiple frequencies from EIM measurements of muscle tissue in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.24 is a series of graphs depicting the measured phase (left panel), reactance (middle panel), and resistance (right panel) of muscle tissue conducted at 2 kHz in wildtype and SOD1G93Azebrafish at 20 weeks of age. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 FIG.25 is a series of graphs depicting the measured phase (left panel), reactance (middle panel), and resistance (right panel) of muscle tissue conducted at 2 kHz in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.26 is a series of graphs depicting the measured phase (left panel), reactance (middle panel), and resistance (right panel) of muscle tissue conducted at 50 kHz in wildtype and SOD1G93Azebrafish at 20 weeks of age. FIG.27 is a series of graphs depicting the measured phase (left panel), reactance (middle panel), and resistance (right panel) of muscle tissue conducted at 50 kHz in wildtype and SOD1G93Azebrafish at 40 weeks of age. FIG.28A is a graph of the measured phase over multiple frequencies from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.28B is a graph of the measured reactance over multiple frequencies from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.28C is a graph of the measured resistance over multiple frequencies from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.29A is a graph of the measured phase conducted at 2 kHz from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.29B is a graph of the measured reactance conducted at 2 kHz from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.29C is a graph of the measured resistance conducted at 2 kHz from EIM measurements of muscle tissue in SOD1G93Azebrafish that were treated with 80 µM glyoxylate or a vehicle control. FIG.30A is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SOD1G93Azebrafish treated with a vehicle control. FIG.30B is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SOD1G93Azebrafish treated with 80 µM of glyoxylate. Scale bar is 100 µm. FIG.30C is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SOD1G93Azebrafish treated with a vehicle control. FIG.30D is a representative micrograph depicting an H&E-stained tissue cross-section of the trunk musculature of SOD1G93Azebrafish treated with 80 µM of glyoxylate. Scale bar is 100 µm. DETAILED DESCRIPTION Described herein are methods of treating a subject (e.g., a mammal, such as a human) that has or is at risk of having skeletal muscle atrophy with compositions comprising glyoxylate or a pharmaceutically acceptable salt thereof. Also described are methods of treating sarcopenia and amyotrophic lateral sclerosis (ALS) in a mammal (e.g., a human) in need thereof by administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof. Advantageously, the methods described herein promote an increase in muscle mass and / or improve muscle function in a subject that has or is at risk of having skeletal muscle atrophy. Without being limited by a mechanism of action, the compositions described herein (e.g., those containing PATENT ATTORNEY DOCKET NO.: 01948-291WO2 glyoxylate) impart therapeutic benefits in a subject with or at risk of developing skeletal muscle atrophy by improving cellular metabolism and energy balance in the subject. In particular, glyoxylate or a pharmaceutically acceptable salt thereof can be administered to modulate cellular and / or subcellular nicotinamide adenine dinucleotide (NAD) and NAD plus hydrogen (NADH) balances or levels thereof, the production or bioavailability of which is generally decreased in aging or damaged tissue. Therefore, administration of a composition described herein improves overall NAD / NADH homeostasis and generates cofactors to support ATP production for improved energy balance and improved skeletal muscle function. The disclosure is based, at least in part, on the discovery that administration of glyoxylate improves muscle mass, muscle composition, and / or overall physical fitness, as determined in zebrafish models of sarcopenia and amyotrophic lateral sclerosis (ALS), which are recognized as animal models of human disease. Due to the highly conserved muscle structure and metabolic pathways and processes between zebrafish and humans, improvements in skeletal muscle mass, skeletal muscle electrophysiology, and physical fitness observed following glyoxylate administration in zebrafish can be extrapolated to human therapy. Consequently, treatment of a human subject that has or is at risk of having muscle skeletal atrophy with a composition that includes glyoxylate or a pharmaceutically acceptable salt thereof can improve the skeletal muscle mass, skeletal muscle electrophysiology, and physical fitness in the treated human subject. I. Treatment indications and subject selection A subject that can be administered a composition described herein includes one that may have skeletal muscle atrophy or be at risk of developing skeletal muscle atrophy, which may, e.g., be caused by any one of several different factors. Such factors include, e.g., age-related skeletal muscle atrophy, underlying immunological or inflammatory illness, underlying neurodegeneration, cellular or mitochondrial dysfunction, a genetic mutation, malnutrition, diminished physical activity, or other factors known in the art. The subject may also be one that exhibits sarcopenia or may be at risk of developing sarcopenia. The subject may also be one that exhibits cachexia or may be at risk of developing cachexia. The subject may be one that exhibits amyotrophic lateral sclerosis (ALS) or may be at risk of developing ALS. The subject may be one that exhibits a muscular dystrophy or may be at risk of developing a muscular dystrophy (e.g., Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, myotonic muscular dystrophy, Limb-Girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, distal muscular dystrophy, or oculopharyngeal muscular dystrophy). The subject may be one that exhibits a congenital myopathy or may be at risk of developing a congenital myopathy (e.g., a core myopathy, a centronuclear myopathy, or a nemaline myopathy). The subject may also be one that exhibits skeletal muscle atrophy for an indeterminant reason. A subject that can be treated according to a method described herein may exhibit skeletal muscle atrophy or be at risk of developing skeletal muscle atrophy due to their age. The subject may be, e.g., between 40 and 95 years of age, or older. For example, the subject may be between 40 and 55 years old (e.g., 40 years old, 41 years old, 42 years old, 43 years old, 44 years old, 45 years old, 46 years old, 47 years old, 48 years old, 49 years old, 50 years old, 51 years old, 52 years old, 53 years old, 54 years old, or 55 years old), between the ages of 55 and 65 years old (e.g., 55 years old, 56 years old, 57 years old, PATENT ATTORNEY DOCKET NO.: 01948-291WO2 58 years old, 59 years old, 60 years old, 61 years old, 62 years old, 63 years old, 64 years old, or 65 years old), between the ages of 65 and 75 years old (e.g., 65 years old, 66 years old, 67 years old, 68 years old, 69 years old, 70 years old, 71 years old, 72 years old, 73 years old, 74 years old, or 75 years old), between the ages of 75 and 85 years old (e.g., 75 years old, 76 years old, 77 years old, 78 years old, 79 years old, 80 years old, 81 years old, 82 years old, 83 years old, 84 years old, or 85 years old), or between the ages of 85 and 95 years old or older (e.g., 85 years old, 86 years old, 87 years old, 88 years old, 89 years old, 90 years old, 91 years old, 92 years old, 93 years old, 94 years old, 95 years old, or older). A subject that can be treated according to a method described herein may exhibit skeletal muscle atrophy or be at risk of developing skeletal muscle atrophy due to an underlying immunological or inflammatory illness, underlying neurodegeneration, cellular or mitochondrial dysfunction, a genetic mutation, malnutrition, diminished physical activity, or other factors known in the art. In some embodiments, the subject is 18 years old or older (e.g., 18 years old, 19 years old, 20 years old, 21 years old, 22 years old, 23 years old, 24 years old, 25 years old, 30 years old, 35 years old, 40 years old, 45 years old, 50 years old, or older). In some embodiments, the subject is a pediatric subject and is younger than 18 years old (e.g., 17 years old, 16 years old, 15 years old, 14 years old, 13 years old, 12 years old, 11 years old, 10 years old, 9 years old, 8 years old, 7 years old, 6 years old, 5 years old, 4 years old, 3 years old, 2 years old, 1 year old, or younger than 1 year old). A subject that can be treated according to a method described herein may be one that exhibits skeletal muscle atrophy or may be at risk of developing skeletal muscle atrophy as determined based on a physical assessment known in the art. A physical assessment of a subject may include weight measurements, body mass measurements (e.g., muscle mass, adipose or fat mass, or a combination thereof), height measurements, and / or determination of a subject’s body-mass index (BMI). In some embodiments, a subject with skeletal muscle atrophy may have a BMI of about 19 kg / m2or lower (e.g., about 19 kg / m2or lower, about 18 kg / m2or lower, about 17 kg / m2or lower, about 16 kg / m2or lower). In some embodiments, a subject having a higher percentage of body fat may be at risk of developing skeletal muscle atrophy. A female subject may be at risk of developing skeletal muscle atrophy if her percentage body fat mass is measured to be about 35% or higher (e.g., about 35% or higher, about 37% or higher, about 40% or higher, or about 43% or higher) relative to, for example, an average percentage body fat mass of a healthy female control subject of about the same age. A male subject may be at risk of developing skeletal muscle atrophy if his percentage of body fat mass is measured to be about 23% or higher (e.g., about 23% or higher, about 25% or higher, about 27% or higher, or about 30% or higher) relative to, for example, an average percentage body fat mass of a healthy male control subject of about the same age. Other physical assessments of a subject may include questions regarding a subject’s lifestyle, such as questions about a subject’s diet and exercise. Other physical assessments may include measuring a muscle mass or muscle quality and / or body fat percentage using electrical impedance myography (EIM), an appendicular skeletal muscle mass (ASMM) assessment by dual-energy X-ray absorptiometry (DXA), whole body skeletal muscle mass (SMM) or ASMM predicted by bioelectrical impedance analysis, a lumbar muscle cross-sectional area assessment determined by a computed tomography (CT) scan or magnetic resonance imaging (MRI). Electrical impedance myography (EIM) values, including low 50 kHz EIM phase or reactance values or elevated resistance values, may be PATENT ATTORNEY DOCKET NO.: 01948-291WO2 consistent with atrophy. Reduced mean myofiber or whole-muscle cross-sectional area measurements can also provide useful quantification of muscle atrophy. EIM and muscle cross-sectional area methodologies and parameters for diagnosing skeletal muscle atrophy (e.g., sarcopenia) are known in the art and have been described elsewhere such as in, e.g., Aaron et al. (Physiol. Meas.27(10):953-959, 2006), Abellan van Kan et al. (J Nutr. Health Aging 15(10):834-846, 2011), and Mitchell et al. (Front. Physiol.11:3:260, 2012), hereby incorporated by reference. Other methods of identifying skeletal muscle atrophy or risk of developing skeletal muscle atrophy in a subject may include performance assessments such as a grip strength test, a chair stand test, a gait speed analysis, a short physical performance battery (SPPB) assessment, a timed-up-and-go test, a 400-meter walk, and / or other assessments known in the art. The European Working Group on Sarcopenia in Older People (EWGSOP2) has developed diagnostic criteria for sarcopenia using some of these physical and performance assessments, and these diagnostic criteria are summarized in Table 1 below, which is adapted from Cruz-Jentoft, et al. (Age and Ageing.48:16-31, 2019), hereby incorporated by reference. Table 1: EWGSOP2 Sarcopenia Diagnostic Criteria A subject may have one or more biological samples extracted for analysis (e.g., a muscle biopsy sample, a blood sample, a urine sample, a saliva sample). The biological sample may be obtained in order to measure a biomarker(s) indicative of skeletal muscle atrophy or a risk of developing skeletal muscle atrophy. Such biomarkers may include metabolites, cofactors, and / or byproducts of the citric acid cycle, among other potential biomarkers described herein. In some embodiments, a level of NAD+ may be used as a biomarker of skeletal muscle atrophy or a risk of developing skeletal muscle atrophy. In some embodiments, a subject has skeletal muscle atrophy when there is a reduction of muscle tissue NAD+ levels of at least 20% (e.g., at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, or more) as compared to a reference muscle tissue sample from a healthy subject. In some embodiments, a subject is at risk of developing skeletal muscle atrophy when there is a reduction of muscle tissue NAD+ levels of about 10% (e.g., about 10%, about 15%, or about 20%) as compared to a reference muscle tissue sample from a healthy subject. In some embodiments, a subject PATENT ATTORNEY DOCKET NO.: 01948-291WO2 has skeletal muscle atrophy when measured levels of NAD+ in muscle tissue are about 0.025 μmol / g of muscle tissue or less (e.g., about 0.025 μmol / g of muscle tissue or less, about 0.020 μmol / g of muscle tissue or less, about 0.015 μmol / g of muscle tissue or less, or less than 0.015 μmol / g of muscle tissue). In some embodiments, the ratio of dinucleotides (i.e., NAD+ / NADH) in cells or subcellular compartments (e.g., the mitochondria, the nucleus, or the cytosol) may be used as a biomarker indicative of skeletal muscle atrophy or a risk of developing skeletal muscle atrophy. Healthy subjects have mitochondrial NAD+ / NADH levels of about 10:1 NAD+ / NADH (Lin and Guarente (Curr. Opin. Cell Biol.15(2):241-246, 2003), Anderson et al. (Biochim Biophys Acta Bioenerg.1858(12):991-998, 2017)). In some embodiments, a subject has or is at risk of developing skeletal muscle atrophy if mitochondrial dinucleotide ratios are lower than healthy levels of about 10:1 NAD+ / NADH (e.g., lower than 10:1 NAD+ / NADH, lower than 9:1 NAD+ / NADH, lower than 8:1 NAD+ / NADH, lower than 7:1 NAD+ / NADH, lower than 6:1 NAD+ / NADH; e.g., about 9:1 NAD+ / NADH, about 8:1 NAD+ / NADH, about 7:1 NAD+ / NADH, about 6:1 NAD+ / NADH, about 5:1 NAD+ / NADH, or lower than 5:1 NAD+ / NADH). Levels of a metabolite or biomarker may be measured via mass spectrometry or other methods to measure levels of a specific analyte relative to a relevant control via biological methods known in the art (e.g., Western blot analysis, ELISA, RT-PCR, colorimetry assays, fluorimetry assays, spectrophotometric assays, an array using targeting antibodies or hybridizing nucleotides, among other similar methods). One or more biological samples may be used for diagnostic purposes and / or for establishing a baseline for a subject prior to administration of the method of treatment. II. Methods of treating skeletal muscle atrophy A. Glyoxylate in cellular respiration Muscle function and energetics are highly dependent on cell metabolism, cell respiration, and redox balance. Aberrations of these regulated cell processes through advancing age, sedentary lifestyle, or other factors generally lead to a decline in muscle mass and function. Glyoxylate and analogs thereof among other related compounds can be administered to a subject in need thereof to restore redox balance in a cell and cellular compartments (e.g., mitochondria). In particular, compositions described herein can be administered to modulate the levels and / or ratio of the oxidized and reduced forms of nicotinamide adenine dinucleotide (i.e., NAD+ / NADH) (FIG.1). By restoring this redox balance, glyoxylate (or a related analog or agent, as described herein) improves cellular and tissue energy metabolism. B. Dosage and administration of glyoxylate Glyoxylate or a pharmaceutically equivalent salt thereof may be administered to a subject in need thereof (e.g., a subject with skeletal muscle atrophy, sarcopenia, cachexia, and / or ALS or at risk of developing skeletal muscle atrophy, sarcopenia, cachexia, and / or ALS) by oral, intravenous, cutaneous, subcutaneous, intradermal, nasal, pulmonary, intramuscular, or intraperitoneal administration. In some embodiments, a composition that includes glyoxylate or an analog thereof is administered to the subject orally. In some embodiments, a composition that includes glyoxylate or an analog thereof is administered to the subject via intramuscular injection. In other embodiments, glyoxylate is administered to the subject via subcutaneous injection. In some embodiments, the route of administration of a composition that includes glyoxylate or an analog thereof can be influenced by a subject’s muscle mass. For example, a PATENT ATTORNEY DOCKET NO.: 01948-291WO2 subject with acute muscle loss may benefit from intramuscular injection of glyoxylate or an analog thereof to address the severity of the muscle loss. By contrast, a subject at risk of muscle loss may be treated with a wider variety of formulations for prophylactic treatment. In some embodiments, the method of treatment can include administration of a liquid formulation of a glyoxylate composition, such as a formulation with a pH of between 3 and 9. In some embodiments, the liquid formulation is administered by injection (e.g., subcutaneous or intramuscular) to a subject at a volume between 300 μL and 1 mL (e.g., between 300 and 400 μL, between 400 and 500 μL, between 500 and 600 μL, between 600 and 700 μL, between 700 and 800 μL, between 800 and 900 μL, or between 900 μL and 1 mL; e.g., 300 μL, 325 μL, 350 μL, 375 μL, 400 μL, 425 μL, 450 μL, 475 μL, 500 μL, 525 μL, 550 μL, 575 μL, 600 μL, 625 μL, 650 μL, 625 μL, 650 μL, 675 μL, 700 μL, 725 μL, 750 μL, 775 μL, 800 μL, 825 μL, 850 μL, 875 μL, 900 μL, 925 μL, 950 μL, 975 μL, or 1 mL). In some embodiments, the liquid formulation is administered at a volume between 1 and 5 mL (e.g., between 1 and 2 mL, between 2 and 3 mL, between 3 and 4 mL, or between 4 and 5 mL; e.g., 1 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2 mL, 2.25 mL, 2.5 mL, 2.75 mL, 3 mL, 3.25 mL, 3.5 mL, 3.75 mL, 4 mL, 4.25 mL, 4.5 mL, 4.75 mL, or 5 mL). In some embodiments, the liquid formulation contains an amount of the glyoxylate composition between 10 mg and 1,000 mg (e.g., between 10 and 50 mg, between 20 and 80 mg, between 50 and 100 mg, between 100 and 150 mg, between 100 and 300 mg, between 100 and 500 mg, between 300 and 500 mg, between 500 and 700 mg, between 500 and 1,000 mg, or between 800 and 1,000 mg; e.g., 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, or 1,000 mg). In some embodiments, the liquid formulation contains an amount of the glyoxylate composition between 1 g and 10 g (e.g., between 1 and 3 g, between 1 and 5 g, between 3 and 5 g, between 5 and 7 g, between 5 and 10 g, between 7 and 9 g, or between 7 and 10 g; e.g., 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, or 10 g). In some embodiments, the liquid formulation contains a concentration of the glyoxylate composition between 1 mM and 1 M (e.g., between 1 and 10 mM, between 10 and 50 mM, between 50 and 100 mM, between 100 and 500 mM, between 500 mM and 1 M; e.g., 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 60 mM, 70 mM, 80 mM, 90 mM, 100 mM, 125 mM, 150 mM, 175 mM, 200 mM, 225 mM, 250 mM, 275 mM, 300 mM, 325 mM, 350 mM, 375 mM, 400 mM, 425 mM, 450 mM, 475 mM, 500 mM, 525 mM, 550 mM, 575 mM, 600 mM, 625 mM, 650 mM, 675 mM, 700 mM, 725 mM, 750 mM, 775 mM, 800 mM, 825 mM, 850 mM, 875 mM, 900 mM, 925 mM, 950 mM, 975 mM, or 1 M). In some embodiments, the glyoxylate composition is a capsule formulation. In other embodiments, the glyoxylate composition is a tablet formulation. In some embodiments, the glyoxylate composition is a formulation with a pharmaceutically acceptable excipient. In some embodiments, a capsule or tablet contains an amount of the glyoxylate composition between 10 mg and 1,000 mg (e.g., between 10 and 50 mg, between 20 and 80 mg, between 50 and 100 mg, between 100 and 150 mg, between 100 and 300 mg, between 100 and 500 mg, between 300 and 500 mg, between 500 and 700 mg, between 500 and 1,000 mg, or between 800 and 1,000 mg; e.g., 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, PATENT ATTORNEY DOCKET NO.: 01948-291WO2 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, or 1,000 mg). In some embodiments, the liquid formulation contains an amount of the glyoxylate composition between 1 g and 10 g (e.g., between 1 and 3 g, between 1 and 5 g, between 3 and 5 g, between 5 and 7 g, between 5 and 10 g, between 7 and 9 g, or between 7 and 10 g; e.g., 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g, 9 g, or 10 g). In some embodiments, the glyoxylate composition is administered as a time-release release formulation. In some embodiments, the time-release formulation has a time lag for release of between about 15 and 90 minutes (e.g., about 15 to 30 minutes, about 30 to 45 minutes, about 45 to 60 minutes, about 60 to 75 minutes, or about 75 to 90 minutes; e.g., about 15 minutes, about 16 minutes, about 17 minutes, about 18 minutes, about 19 minutes, about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, about 60 minutes, about 65 minutes, about 70 minutes, about 75 minutes, about 80 minutes, about 85 minutes, or about 90 minutes). In some embodiments, the time-release formulation has a time lag for release of about 2 hours to about 5 hours (e.g., about 2 hours, about 3 hours, about 4 hours, about 5 hours, or longer than 5 hours). In other embodiments, the time release formulation has a time lag for release of about 5 hours to about 12 hours (e.g., about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, or longer than 12 hours). Glyoxylate may be administered to a subject in need thereof at a dose that can be determined based on the subject’s weight or body mass. In some embodiments, glyoxylate is administered to the subject at a dose between 1 and 10 mg / kg (e.g., between 1 and 3 mg / kg, between 3 and 5 mg / kg, between 5 and 7 mg / kg, between 7 and 9 mg / kg, or between 8 and 10 mg / kg; e.g., 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg). In some embodiments, glyoxylate is administered to the subject at a dose of less than 5 mg / kg (e.g., less than 5 mg / kg, less than 4 kg / mg, less than 3 mg / kg, less than 2 mg / kg, or less than 1 mg / kg). Alternatively, glyoxylate can be administered to a subject in need thereof at a fixed dose in a range of between 30 mg and 300 mg (e.g., between 30 and 50 mg, between 50 and 100 mg, between 100 and 150 mg, between 150 and 200 mg, between 200 and 250 mg, or between 250 and 300 mg; e.g., 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, or 300 mg). In some embodiments, glyoxylate can be administered at a fixed dose in a range of between 250 mg and 1,000 mg (e.g., between 250 and 500 mg, between 500 and 750 mg, or between 750 and 1,000 mg; e.g., 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, or 1,000 mg). In some embodiments, glyoxylate can be administered at a fixed dose in a range of between 1 g and 5 g (e.g., between 1 and 2 g, between 2 and 3 g, between 3 and 4 g, between 4 and 5 g; e.g., 1 g, 1.25 g, 1.5 g, 1.75 g, 2 g, 2.25 g, 2.5 g, 2.75 g, 3 g, 3.25 g, 3.5 g, 3.75 g, 4 g, 4.25 g, 4.5 g, 4.75 g, or 5 g). A composition that includes glyoxylate or an analog thereof can be administered to a subject in need thereof at least once per day, week, or month. For example, glyoxylate can be administered to the subject at least once daily (e.g., 1 time daily, 2 times daily, 3 times daily, or more than 3 times daily). If PATENT ATTORNEY DOCKET NO.: 01948-291WO2 administered more than once daily, the composition can be administered every hour, every two hours, every three hours, every four hours, every five hours, every six hours, every seven hours, every eight hours, every nine hours, every ten hours, every eleven hours, or every twelve hours, or more. In some embodiments, glyoxylate is administered to the subject every other day. The composition can be administered at least once per week (e.g., 1 time per week, 2 times per week, 3 times per week, 4 times per week, 5 times per week, 6 times per week, 7 times per week, or more than 7 times per week). In some embodiments, glyoxylate is administered as a single dose. In other embodiments, glyoxylate is administered in multiple, separate doses (e.g., 2 separate doses, 3 separate doses, or more than 3 separate doses). The duration of treatment with glyoxylate or an analog thereof may be a number of days, a number of weeks, a number of months, a number of years, or indefinitely. In some embodiments, a subject is treated with glyoxylate or an analog thereof for 21 days or less (e.g., less than 21 days, less than 20 days, less than 19 days, less than 18 days, less than 17 days, less than 16 days, less than 15 days, less than 14 days, less than 13 days, less than 12 days, less than 11 days, less than 10 days, less than 9 days, less than 8 days, less than 7 days, less than 6 days, less than 5 days, less than 4 days, or less than 3 days). In some embodiments, a subject is treated with glyoxylate or an analog thereof for 2 weeks or longer (e.g., longer than 2 weeks, longer than 3 weeks, longer than 4 weeks, longer than 5 weeks, longer than 6 weeks, longer than 7 weeks, or longer than 8 weeks). In some embodiments, a subject is treated with glyoxylate or an analog thereof for at least one month (e.g., at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or longer). In some embodiments, a subject is treated with glyoxylate for about 1 to 3 years (e.g., about 1 year, about 2 years, about 3 years). In some embodiments, a subject is treated with glyoxylate or an analog thereof for over a year (e.g., 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, or longer than 10 years). In other embodiments, a subject is treated with glyoxylate or an analog thereof indefinitely. C. Monitoring and determining the efficacy of treatment Determining the efficacy of a method of treatment with a composition comprising glyoxylate or a pharmaceutically equivalent salt thereof or an analog thereof may require evaluating the subject’s response to the treatment. The subject’s response may be evaluated in an in-patient treatment setting or an out-patient treatment setting. Evaluation of the subject’s response may occur one or more times following administration of the composition or during the treatment regimen. Evaluation of the subject’s response may occur continuously, either sporadically or at designated time points following administration of the composition. Evaluation of the subject’s response may occur, for example, 1-10 days after administration of the composition (e.g., 7-10 days, 6-8 days, 5-7 days, 3-5 days, 2-4 days, 1-3 days, or within 1 day following administration of the composition; e.g., 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, 1 day, or less than a day following administration of the composition). Evaluation of the subject’s response may occur 1-12 weeks or more after administration of the composition (e.g., 10-12 weeks, 8-12 weeks, 6-12 weeks, 8-10 weeks, 6-10 weeks, 4-10 weeks, 6-8 weeks, 4-8 weeks, 2-8 weeks, 4-6 weeks, 2-6 weeks, 3-6 weeks, 2-4 weeks, 1-3 weeks, or 1-2 weeks PATENT ATTORNEY DOCKET NO.: 01948-291WO2 following administration of the composition; e.g., later than 12 weeks, 12 weeks, 11 weeks, 10 weeks, 9 weeks, 8 weeks, 7 weeks, 6 weeks, 5 weeks, 4 weeks, 3 weeks, 2 weeks, or 1 week following administration of the composition). Evaluation of the subject’s response may occur 1-12 months after administration of the composition (e.g., 10-12 months, 8-10 months, 6-8 months, 4-6 months, 3-5 months, 2-4 months, or 1-3 months following administration of the composition; e.g., 12 months, 11 months, 10 months, 9 months, 8 months, 7 months, 6 months, 5 months, 4 months, 3 months, 2 months, or 1 month following administration of the composition). Evaluation of the subject’s response may occur 1-5 years or longer after administration of the composition (e.g., 4-5 years, 3-5 years, 2-3 years, or 1-3 years following administration of the composition; e.g., later than 5 years, 5 years, 4 years, 3 years, 2 years, or 1 year following administration of the composition). Evaluation of the subject’s response may involve determining an increase in muscle mass or an increase in physical strength of the subject. Determining an increase in muscle mass or physical strength may be done via one or more methods of assessment described herein (e.g., EIM, a grip strength test, a chair stand test, an ASMM assessment by DXA, whole body SMM or ASMM predicted by bioelectrical impedance analysis, a lumbar muscle cross-sectional area assessment determined by a CT scan or MRI, a gait speed analysis, a short physical performance battery (SPPB) assessment, a timed-up-and-go test, a 400-meter walk, or a combination thereof). In some embodiments, an evaluation of a subject’s response to treatment shows a mild increase in muscle mass or physical strength. A mild increase in muscle mass or physical strength may be defined by at least a 5% increase as determined by one or more of the foregoing parameters. A mild increase in muscle mass or physical strength may be a 5% increase, a 10% increase, or more. A mild increase in muscle mass or physical strength may indicate an increase in dose of the administered treatment such that the dose is increased by at least 20% (e.g., at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or greater than 100%) relative to a previous dose. A mild increase in muscle mass or physical strength may indicate a need for an increase in frequency of treatment administration (e.g., an increase of at least one more time per day, at least one more time per week, at least one more time per month, or more). A mild increase in muscle mass or physical strength may indicate a need for the administration of one or more combination therapies, as discussed in the following section. In some embodiments, a subject in need thereof that is administered the method of treatment exhibits a moderate increase in muscle mass or physical strength (e.g., based on an evaluation of a subject’s response to treatment using one or more of the metrics described herein). A moderate increase in muscle mass or physical strength may be at least a 20% increase in one or more of the foregoing parameters. A moderate increase in muscle mass or physical strength may be a 20% increase, a 25% increase, a 30% increase, a 35% increase, a 40% increase, a 45% increase, or more relative to the muscle mass or physical strength of the subject prior to treatment or relative to a control or reference subject. A moderate increase in muscle mass or physical strength may indicate continued therapy with no change to the method of treatment. A moderate increase in muscle mass or physical strength may indicate a need for an increase in the dose of the administered treatment such that the dose is increased by at least 10% (e.g., at least 10%, at least 20%, at least 30% at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or greater than 100%) relative to a previous dose PATENT ATTORNEY DOCKET NO.: 01948-291WO2 administered to the subject. A moderate increase in muscle mass or physical strength may indicate a need for an increase in frequency of treatment administration (e.g., an increase of at least one more time per day, at least one more time per week, at least one more time per month, or more). A moderate increase in muscle mass or physical strength may indicate a need for the administration of one or more combination therapies, as discussed in the following section. In some embodiments, an evaluation of a subject’s response shows a high increase in muscle mass or physical strength (e.g., based on an evaluation of a subject’s response to treatment using one or more of the metrics described herein). A high increase in muscle mass or physical strength may be defined by at least a 50% increase in one or more of the foregoing parameters. A high increase in muscle mass or physical strength may be a 50% increase, a 60% increase, a 70% increase, an 80% increase, a 90% increase, or more relative to the muscle mass or physical strength of the subject prior to treatment or relative to a control or reference subject. A high increase in muscle mass or physical strength may indicate a need for continued therapy with no change to the method of treatment. A high increase in muscle mass or physical strength may indicate a need for a decrease in dose of the administered treatment such that the dose is decreased by about 50% (e.g., about 50%, about 40%, about 30%, about 20%, or about 10%) relative to a previous dose administered to the subject. A high increase in muscle mass may indicate a reduction in the frequency of treatment administration such that the frequency of treatment is reduced by at least one time per month, one time per week, or one time per day, depending on the frequency of treatment administration. Evaluation of the subject’s response to the treatment method may also include testing a biological sample from the subject. The biological sample may be a muscle tissue biopsy, blood or a blood component (e.g., plasma, serum, or isolated circulating components such as cells), a saliva sample, or a urine sample. The biological sample may be used to measure the levels of one or more metabolites or biomarkers (e.g., NAD+). Levels of a metabolite or biomarker may be measured via mass spectrometry or other methods to measure levels of a specific analyte relative to a relevant control via biological methods known in the art (e.g., Western blot analysis, ELISA, RT-PCR, colorimetry assays, fluorimetry assays, spectrophotometric assays, an array using targeting antibodies or hybridizing nucleotides, among other similar methods). Measurements derived from a biological sample may be compared to a previously measured baseline (e.g., upon diagnosis or prior to the administration of the method of treatment) or may be used to continuously measure the subject’s response to treatment. In some embodiments, a level of NAD+ in muscle tissue is used as a biomarker to assess therapeutic effectiveness. In some embodiments, a subject shows a mild increase in muscle tissue NAD+ such that there is about a 5% increase (e.g., about 5%, about 7%, or about 10%) as compared to NAD+ levels prior to treatment. In some embodiments, a subject shows a moderate increase in muscle tissue NAD+ such that there is about a 10% increase (e.g., about 10%, about 12%, about 15%, or more) as compared to NAD+ levels prior to treatment. A mild or moderate increase in NAD+ level may indicate a need for an increase in the dose of treatment by at least 20% (e.g., at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or greater than 100%) relative to a prior dose. A mild or moderate increase in NAD+ level may indicate a need for an increase in the frequency of treatment administration (e.g., at least one more time per day, at least one more time per week, at least one more time per month, or more). A mild or moderate increase in NAD+ PATENT ATTORNEY DOCKET NO.: 01948-291WO2 level may indicate the need to supplement the treatment with one or more combination therapies (as discussed in the following section). In some embodiments, a subject shows a high increase in muscle tissue NAD+ such that there is about a 15% increase in muscle tissue NAD+ (e.g., about 15%, about 20%, about 25%, about 30%, or higher). In some embodiments, a subject shows a high increase in muscle tissue NAD+ levels if the levels are within about 10% of a reference muscle tissue sample from a healthy subject. A high increase in muscle tissue NAD+ levels may indicate that the subject would benefit from continued therapy with no change to the method of treatment. A high increase in muscle tissue NAD+ levels may indicate that a reduction in the dose (e.g., the amount or concentration of glyoxylate or an analog thereof) of the administered treatment could be implemented without loss of efficacy, such as reduction in the dose of about 50% (e.g., about 50%, about 40%, about 30%, about 20%, or about 10%) relative to a previous dose. A high increase in muscle tissue NAD+ levels may indicate that a reduction in the frequency of treatment administration could be implemented without loss of efficacy, such as a reduction in the frequency of the administered treatment of at least one time per month, one time per week, or one time per day, depending on the frequency of treatment administration. III. Combination therapies A subject being treated for skeletal muscle atrophy, sarcopenia, cachexia, and / or ALS or a risk thereof, may also be administered or subjected to one or more additional forms of therapy to treat or reduce the likelihood of developing the skeletal muscle atrophy, sarcopenia, cachexia, and / or ALS. For example, one or more combination therapies can be administered at the start of treatment with a pharmaceutical composition comprising glyoxylate or a pharmaceutically equivalent salt thereof or an analog thereof. In some embodiments, one or more combination therapies can be administered after the administration of the pharmaceutical composition. Alternatively, or in addition, the one or more combination therapies can be administered prior to treatment with the pharmaceutical composition. Such additional forms of therapy may include one or more of exercise, a nutrition or dietary program, electrical stimulation therapy, and administration of an additional therapeutic agent(s). Each of these additional forms of therapy are described below. A. Exercise A subject in need of treatment for skeletal muscle atrophy, sarcopenia, cachexia, and / or ALS, or a risk thereof, may be subjected to an exercise(s) as a form of combination treatment. In some instances, the form of exercise may be part of an exercise regimen determined by a physical therapist, physician, exercise trainer, or another skilled practitioner. The form of exercise may be a resistance training exercise regimen and / or an aerobic training exercise regimen known in the art. The resistance training exercise regimen may include low-load resistance training or higher-load resistance training, depending on the weight and strength of the subject. In some instances, the form of exercise requires equipment such as hand-held weights, resistance bands, exercise machinery, among other forms of equipment. In some embodiments, the timing and frequency of a form of exercise may be determined by a physical therapist, physician, exercise trainer, or another skilled practitioner. The form of exercise may be performed over a set period of time, such as over the course of a year, over the course of several years, over the course of a month, over the course of several months, over the course of a week, over the PATENT ATTORNEY DOCKET NO.: 01948-291WO2 course of several weeks, over the course of a day, or over the course of several days. In some instances, the form of exercise may be performed one or more times a week, such as seven times a week, six times a week, five times a week, four times a week, three times a week, two times a week, or one time a week. In some instances, the form of exercise may be performed one or more times a day, such as one time a day, two times a day, three times a day or more. The duration of exercise sessions, frequency of exercise sessions, and / or types of exercise performed may change over time based on a subject’s capability and / or improvement. B. Nutrition or dietary program The combination therapy used to treat skeletal muscle atrophy, sarcopenia, and / or cachexia may include a nutrition or dietary program. The nutrition or dietary program may be determined by a physician, a nutritionist or dietary specialist, a healthcare specialist, or another skilled practitioner. The duration of the nutrition or dietary program and / or the recommended nutritional composition may be adjusted based on improvements or changes to the subject’s muscle mass and / or body weight or other dietary needs. A nutrition or dietary program may include changes to the subject’s daily calorie intake. A nutrition or dietary program may include a diet consisting of a determined nutritional composition. The nutritional composition may be specific guidelines for daily intake of nutrients that may include considerations for protein, carbohydrates, fat (e.g., unsaturated fats and / or saturated fats), fiber, vitamins, micronutrients, and / or levels of hydration. A nutrition or dietary program may include changes to the subject’s nutritional composition through dietary changes or nutritional supplements such as vitamins (e.g., vitamin D, vitamin E, vitamin A, vitamin K, vitamin B, among others), amino acids (leucine, glycine, arginine, tryptophan, proline, among others), minerals (e.g., zinc, copper, manganese, among others), creatine or other micronutrients or compounds. A nutrition or dietary program may include changes to the subject’s daily intake of protein by dietary changes and / or protein supplements or concentrates (e.g., whey protein, protein powders, protein shakes, and / or other examples of protein supplements or concentrates). A nutrition or dietary program may include a high-protein diet with recommended daily protein intake according to guidelines known in the art. A nutrition or dietary program may include a nutritional composition with high leucine content with a recommended daily leucine intake according to guidelines known in the art. Guidelines to nutritional compositions directed to those with skeletal muscle atrophy is known in the art and can be found, for example, in U.S. Patent No.11,612,578, incorporated herein by reference. C. Electrical stimulation therapy The combination therapy may also include a form of electrophysical therapy or electromyostimulation. Electromyostimulation is a form of therapy in which surface electrodes are applied to the skin such that they are over the motor point of the muscle (i.e., where the muscle has the highest excitability or contraction) and electrical stimulus is applied to the muscle with the goal of increasing muscle mass and / or muscle function. The electromyostimulation may be performed intermittently or chronically. The electromyostimulation may be performed over a period of days, over a period of weeks, over a period of months, or over a period of years. Methods directed to electromyostimulation are known PATENT ATTORNEY DOCKET NO.: 01948-291WO2 in the art and are illustrated elsewhere. See, e.g., Pette and Vrbova (Rev. Physiol. Biochem., 120:115- 202, 2005) and Benavent-Caballer et al. (Exp. Gerontol., 58:159-165, 2014), hereby incorporated by reference. D. Citric acid cycle intermediates or metabolites with structural similarities to glyoxylate In some instances, the combination therapy may include a composition comprising any one or more citric acid cycle intermediates. The one or more intermediates selected for use as a composition for combination therapy may augment levels of NAD+ or NADH of a cell as shown in FIGS.2 and 3. These intermediates selected for use as a composition for combination therapy may include one or more compounds selected from pyruvate, alanine, isocitrate, or a combination thereof. Other forms of combination therapy may include a composition comprising a metabolite with structural similarities to glyoxylate. The metabolite may be administered as a salt or zwitterionic form in which the compound has no net positive or negative charge. The metabolite may include a compound or a pharmaceutically equivalent salt thereof selected from glyceraldehyde, glyoxal, pyruvate, oxaloacetate, methylglyoxal, alpha-ketobutyrate, alpha-ketoglutarate, 3-methyl-2-oxovaleric acid, dihydroxyacetone, acetaldehyde, oxalate, glycolate, malate, lactate, or a combination thereof. E. Additional molecules selected for combination therapy In some embodiments, the form of combination therapy may include a method of treatment with a composition comprising a molecule that targets an alternative biological pathway to glyoxylate or a pharmaceutically equivalent salt thereof (FIG.4). In some embodiments, the additional therapeutic agent includes a composition comprising β- aminoisobutyric acid (BAIBA), an enantiomer, or a pharmaceutically equivalent salt thereof. BAIBA is a metabolite regulator of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which is a key metabolic regulator of skeletal muscle health. BAIBA improves oxygen consumption and modulates insulin sensitivity and skeletal muscle glucose similar to values found in healthy tissue. Further, BAIBA improves skeletal muscle function via AMP-activated protein kinase (AMPK) and peroxisome proliferator- activated receptor delta (PPAR-δ). BAIBA is highly water soluble and may be administered using the same delivery method as glyoxylate or a pharmaceutically equivalent salt thereof. In some embodiments, the additional therapeutic agent includes a composition comprising a cyclobutane-scaffold-based molecule. A cyclobutane-scaffold-based molecule activates the silent information regulator 1 (SIRT1) pathway, a pathway that modulates the inflammatory response and other processes such as gluconeogenesis, glycolysis, insulin sensitivity, fatty acid oxidation, and cholesterol metabolism. Cyclobutane-scaffold-based molecules may be synthesized as described in, e.g., Telmesani et al. (Angew Chem Int Ed Engl., 54:11521-11525, 2015) and Lenihan et al. (Org. Process Res. Dev., 26:1812-1819, 2022), each of which is hereby incorporated by reference. Such cyclobutane-scaffold- based molecules may be administered in conjunction with a steroid or another vehicle for administration. Exemplary effect of a cyclobutane-scaffold-based molecule on myotube diameter is shown in FIG.5. In some embodiments (e.g., in a method for treating ALS in a subject (e.g., a human) in need thereof with glyoxylate or a pharmaceutically acceptable salt thereof), the additional therapeutic agent comprises one or more therapeutic agents for the treatment for ALS. A therapeutic agent for the PATENT ATTORNEY DOCKET NO.: 01948-291WO2 treatment of ALS may be a small molecule. A therapeutic agent for the treatment of ALS may be an inhibitory nucleic acid (e.g., an antisense oligonucleotide or a small interfering RNA) that targets a gene associated with ALS (e.g., C9ORF72, SOD1, TARDBP, FUS, PFN1, NEFH, PRPH, or DCTN1). A therapeutic agent for the treatment of ALS may be an antibody or antigen-binding fragment thereof that targets a protein identified as a target for ALS (e.g., SOD1, TAR DNA binding protein 43 (TDP43), C9ORF72, neurite outgrowth inhibitor (NOGO)-A, NOGO-B, NOGO-C, interleukin 6 receptor (IL6R), myostatin, neuropilin-1, among other proteins known in the art). Exemplary protein targets and antibodies are disclosed elsewhere, e.g., Poulin-Brière, et al. (Front Neurosci.15:790114, 2021), which is hereby incorporated by reference. Additional exemplary therapeutic agents for the treatment of ALS are edaravone (CAS No.89-25-8; RADICAVA ORS® [Mitsubishi Tanabe Pharma America, Inc.]), dextromethorphan hydrobromide and quinidine sulfate (CAS No.632366-89-3; NUEDEXTA® [Otsuka America Pharmaceutical, Inc.]), riluzole (CAS No.1744-22-5; RILUTEK® [Sanofi]), and tofersen (CAS No.2088232-70-4; QALSODY® [Biogen]). EXAMPLES Example 1. Zebrafish as an animal model of skeletal muscle atrophy Zebrafish have many unique advantages for the assessment of progressive muscle atrophy, e.g., sarcopenia. They are inexpensive and easy to breed and age in large volumes at high density, with individuals costing only a few dollars and a typical female laying 200 eggs per week. Thousands of adult animals can be inexpensively housed in a modest footprint by a single investigator. Their genetics have been well delineated with their genome fully characterized in 2013. Due to their genetic and physiological similarities to humans, zebrafish are a well-established vertebrate organism to study human diseases. Moreover, because disease proteins and processes are conserved between humans and zebrafish, drug targets are conserved which enables therapeutic discovery. Zebrafish are genetically also easy to manipulate including using CRISPR and other technologies. Even cognition can be studied. Additionally, zebrafish are very easy to dose when administering potential therapeutic compositions and controls. Whereas most drugs are administered orally and intraperitoneally in mice, zebrafish are dosed simply by placing the animals in a separate smaller tank containing the dissolved drug which is absorbed through their gills, skin, and intestines. Alternatively, for molecules with poor aqueous solubility, they can be simply turned into edible food pellets without any specialized equipment. Obtaining data on large quantities of individual animals opens the possibility of using machine-learning techniques to optimize analysis, a far more challenging prospect in rodents or humans, where the number of individuals under study is often low. There is an especially high degree of conservation between humans and zebrafish in molecular and physiological pathways that regulate skeletal muscle biology. They model human muscle well in that they contain major categories of slow- and fast-twitch fibers (Types 1 and 2) and satellite cells. A unique advantage is the fact that most of the body is muscle and fiber types are completely separated anatomically, with Type 2, fast-twitch fibers occupying most of the dorsal and ventral regions and Type 1, slow-twitch fibers occupying the lateral regions (FIG.6A). This greatly simplifies assessment of therapies that impact fiber-types differently, which has been a challenge in other models. They are straightforward PATENT ATTORNEY DOCKET NO.: 01948-291WO2 to evaluate via swimming performance metrics and new electrophysiological techniques, as described below. Changes in muscle composition can be evaluated with age. Through their lifespan, zebrafish experience a senescence-related decline in physical ability and skeletal muscle architecture like that observed in humans and mammalian aging models. Such decline can be measured via changes in muscle morphology, swimming performance, and EIM measurements described herein and summarized in Table 2 below. Table 2: Primary Biomarkers or Measures of Interest Example 2: Morphology changes in age-related skeletal muscle atrophy in zebrafish Experimental methods Cross-sectional images of the caudal trunk skeletal muscle were captured on a Keyence BZ- X710 Imaging Platform. The cross-sectional area, cell perimeter, and space between myofibers were measured using the hybrid cell counting tool. Automated segmentation was curated for accuracy. Incorrectly segmented features were manually adjusted using the fine edit tool. Six images of epaxial caudal muscle per animal were analyzed; 600-1800 myofibers were analyzed per animal. Type 1 and Type 2 fibers are anatomically separate and both groups were assessed. Connective tissue was quantified via Mason Trichrome stained tissue sections in ImageJ using the MTS color deconvolution tool. PAX7 staining was used to quantify satellite cells. Blood vessel density was assessed by CD31 staining. All tissues including bone, skeletal muscle, and brain were frozen for potential future use. Results Young zebrafish exhibited large polygonal-shaped myofibers sheathed in a layer of ordered endomysium (connective tissue), while aged zebrafish exhibit smaller myofibers with disordered endomysium and increased extracellular space (FIGS.6B-6D). Morphometric features of fibers were quantified in image analysis software. Mean cross-sectional fiber area and fiber perimeter were reduced in aged animals as compared to young animals (676 ± 383 versus 1304 ± 128 μm2, p=0.004; and 104 ± 30 versus 159 ± 7 μm, p=0.0005, respectively, FDR≤0.05). Aged animals exhibited increased extracellular space between myofibers as compared to young animals (44 ± 6 % versus 25 ± 4 % of total area, p=0.0005, FDR≤0.05). Together, these morphometric features of muscle architecture demonstrate age-dependent muscle alterations in Tübingen zebrafish, similar to those observed in aged mammals. Example 3: Swimming performance assays to detect muscle atrophy in zebrafish Zebrafish exhibit a robust repertoire of stereotypical motor traits. Several parameters of swimming performance have been successfully used to assess muscle function in zebrafish models of muscular dystrophies; however, few studies have evaluated these metrics in the context of sarcopenia. Swimming performance and body kinematics can be assessed by measuring basal motor movements. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Experimental methods Animals were first acclimated to an enclosed, no-flow testing arena for 60 minutes, where a 20- minute video (collecting 30 frames / second) was acquired. Data were collected simultaneously on 10 animals in individual tanks using an overhead telecentric lens. Individual animals are segmented and basal activity and motor traits are measured using EthoVision XT 17 Behavioral Tracking software (FIGS. 7A-7C). Endpoints include velocity, angular velocity, acceleration, turn angle, non-displacement motion, and total distance traveled. Results To evaluate the impact of aging on motor traits, we captured digital videos of zebrafish and, using animal tracking software, quantified 6 parameters including turn angle, angular velocity, and lateral motion (FIGS.7A-7L). Aged zebrafish exhibited decreased total distance traveled (784 ± 332 versus 1409 ± 302 cm; p=0.003), decreased velocity (6.5 ± 3.0 versus 11.9 ± 3.9 cm / s; p=0.002), and decreased acceleration (7.0 ± 2.9 versus 16.6 ± 6.2 cm / s2; p=0.002) as compared to young zebrafish (all FDR≤0.05). Young zebrafish were capable of body maneuvers that resulted in deeper turn angles as compared to aged fish (16.9 ± 3.5 versus 9.7 ± 2.7 degrees, p=0.0003, FDR≤0.05) (FIGS.7D-7F). In addition, young fish exhibited greater angular velocity as compared to aged fish, indicating that it takes more time for aged fish to change their direction of travel (163.5 ± 35.0 versus 72.4 ± 30.7 degrees / s, p=0.0003, FDR≤0.05) (FIGS.7G-7I). Aged zebrafish exhibited decreased lateral motion, i.e., non- displacement motion, as compared to young zebrafish (29.8 ± 9.2% versus 58.6 ± 11.1% change in body area, p=0.0006, FDR≤0.05); FIGS.7J-7L). In sum, these findings demonstrate that aged zebrafish exhibit alterations in stereotypic motor traits as compared to young zebrafish which result from weak, short- duration movements of aged fish as compared to fast, vigorous movements of young fish. Example 4: EIM measurements to monitor age-related muscle atrophy Surface EIM can detect altered phase angle, reactance, and resistance in the caudal muscles of aged zebrafish and can provide a surrogate measure of muscle condition. Further, non-invasive surface EIM detects alterations can be observed in sarcopenia as exemplified below. Experimental methods The day prior to the assay, 8 scales were plucked from the epaxial caudal musculature just below the dorsal fin – a morphological landmark that was used to consistently position the electrode array in the same region (FIG.8A). EIM was applied via the mView system (MYOLEX®, Inc., Boston, MA) with custom zebrafish adaptors (FIG.8B). The data were acquired in <1 minute during which 4 serial measurements are captured, after which the animal is returned to their home tank. Relationships between muscle impedance gathered from EIM data and muscular composition in healthy and sarcopenic muscle are summarized in FIG.8C. Endpoints focus on 2 kHz EIM values which we have identified as strongly correlated with muscle atrophy in aged animals versus young animals. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Results Surface EIM multifrequency data were collected in the epaxial caudal muscles of young (8 months) and aged zebrafish (36 months) (n=17). In aged animals, there was a trend toward decreased phase at low frequencies (<10 kHz) (FIG.9A), decreased reactance at almost all frequencies (FIG.9B), decreased resistance at frequencies <60 kHz, and increased resistance at high frequencies (250 kHz) (FIG.9C). In single frequency analyses, the most significant findings were at 2 kHz phase (p<0.000001, q=<0.01) (FIG.9D), and 2 kHz reactance (p=0.000004, q=<0.01) (FIG.9E), followed by 2 kHz resistance (p= 0.0008, q=<0.01) (FIG.9F). EIM data of a second independent cohort of young and aged animals demonstrated similar findings. Moreover, cross-sectional myofiber area correlates with surface EIM measurements in zebrafish skeletal muscle. In rodent animal and human models, electrical impedance correlates with histological and morphometric features of muscle fibers. We evaluated the correlation between zebrafish surface EIM values and cross-sectional myofiber area, as assessed by morphometric analysis on skeletal muscle tissue sections from zebrafish (n=50). Strong associations were found between myofiber size and 2 kHz phase (r=0.831; p=2E-012) (FIG.9G), 2 kHz reactance (r=0.6959; p=2E-008) (FIG.9H), and 2 kHz resistance (r=0.7220; p=4E-009) (FIG.9I). Nominally significant findings were also observed at other frequencies. These data confirm that EIM can be used to assess skeletal muscle atrophy in a subject in need thereof, as well as changes in skeletal muscle tissue, e.g., following a treatment regimen, as described herein. Example 5: Glyoxylate improves condition of sarcopenic skeletal muscle We tested glyoxylate, an endogenous, cell membrane-permeable, intermediary metabolite that generates both NADH and NAD+ cofactors via its capability to be either oxidized or reduced to evaluate potential improvements in skeletal muscle health in zebrafish with sarcopenia. Aged zebrafish (36 months, ~75-85% lifespan) were treated daily for four weeks with glyoxylate (80 μM or 10 μM where indicated). Glyoxylate is delivered to the zebrafish by dissolving the compound in the water that bathes the fish, wherein the zebrafish absorb the compound through the gill epithelium, skin, and gut during a two-hour exposure. EIM was performed according to the method descriptions provided in Example 4. Glyoxylate normalized EIM values (FIGS.10A-10F) and myofiber size in sarcopenic animals (FIGS.11A and 11B; p<0.0001). These data confirm that glyoxylate can be used to treat skeletal muscle atrophy in a subject in need thereof. Example 6: Methods of metabolomic profiling in zebrafish samples By using the most sensitive triple quadrupole mass spectrometer available (Agilent 6490) our analytical methods consume only 3 μL zebrafish plasma or 2 mg zebrafish tissue and are ideal for these small animals. Minimally invasive blood sampling is obtained from the dorsal aorta of fasted fish, in which about 10 to 15 μL of blood is collected and spun down to collect plasma. Animals are weighed prior to blood collection. Our platform uses targeted, multiple reaction monitoring-based LC-MS / MS (liquid chromatography tandem mass spectrometry) to measure ~500 endogenous metabolites using 3 methods PATENT ATTORNEY DOCKET NO.: 01948-291WO2 shown in Table 3 below. Briefly, metabolites are extracted using acetonitrile and methanol, and samples are spiked with deuterated internal standards for quality control. The extracts are separated using reverse-phase chromatography and detected by a coupled 6490-QQQ iFunnel mass spectrometer (Agilent) or 4000 QTRAP mass spectrometer (Sciex, Framingham, MA), depending on the method. Metabolite quantification is determined by integrating peak areas using MassHunter QQQ Quant (Agilent, Santa Clara, CA) and MultiQuant (Sciex). The coefficient of variations (CVs) for analyte measurements are generally ≤15%, and closer to 6% for abundant analytes such as amino acids. Metabolite pathway analysis is performed in MetabolAnalyst 3.5. Examples of mass spectrometry methods and metabolites of interest for metabolomic studies are outlined in Table 3. Table 3: Mass Spectrometry Metabolomics Example 7: Treatment of a subject at risk of skeletal muscle atrophy A 65-year old female subject is determined to be at risk of developing skeletal muscle atrophy. The subject can be administered glyoxylate treatment to maintain skeletal muscle mass and physical ability as she ages. She can self-report her physical strength and abilities during the treatment regimen, and her muscle tissue can be assessed through physical examination and EIM. The subject may have adiposity and measured muscle resistance and reactance parameters consistent with a generally healthy 65-year old adult female. The subject may receive, for example, 1 to 5 mg / kg glyoxylate by subcutaneous injections every other day to maintain muscle mass and muscle function. At several subsequent doctor’s appointments, the subject’s physician may take EIM measurements and perform physical examinations. The subject’s physician may report increased muscle mass and stabilized EIM measurements as compared to the subject’s values prior to glyoxylate treatment and, for example, as compared to a 65- year old female that did not receive glyoxylate treatment. Example 8: Treatment of a subject with skeletal muscle atrophy A 75-year old male subject with skeletal muscle atrophy (e.g., sarcopenia), as determined by diminished mobility, a decrease in muscle mass over at least a year, and reduced strength over time, can be administered twice weekly intramuscular injections of glyoxylate. The subject can be administered a PATENT ATTORNEY DOCKET NO.: 01948-291WO2 single dose of glyoxylate in an amount of 1 to 10 mg / kg (e.g., 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg). The subject can be assessed for improved muscle mass, mobility, and muscle strength, for example, via EIM, a grip strength test, and / or a short physical performance battery (SPPB). Improvement in one or more of these metrics, as compared to the measurements collected prior to glyoxylate treatment, indicates treatment of the sarcopenia. Example 9: Treatment of a subject with skeletal muscle atrophy due to a muscular dystrophy A 4-year old male subject is determined to have a muscular dystrophy (e.g., Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, myotonic muscular dystrophy, Limb-Girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, distal muscular dystrophy, or oculopharyngeal muscular dystrophy), as determined by a skilled practitioner based on the subject’s difficulty walking, weakness in the facial muscles, and / or a genetic test. The subject can be administered a twice daily dose of 10 mg to 1,000 mg glyoxylate in a tablet formulation. The glyoxylate can be administered is a combination therapy with an additional treatment (e.g., a physical therapy program). The subject can be assessed for improved muscle mass, mobility, and muscle strength via EIM and physical examinations. The subject’s physician may report increased muscle mass and stabilized EIM measurements as compared to the subject’s values prior to glyoxylate treatment, for example, as compared to an age-matched subject with a muscular dystrophy that did not receive the treatment. Example 10: Zebrafish as an animal model of amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. ALS is classified by cause into two groups: heritable ALS and sporadic ALS. Among the genetic cases, the most common mutations are in superoxide dismutase 1 (SOD1), TAR DNA binding protein (TARDBP), chromosome 9 open reading frame 72 (C9ORF72), and FUS RNA binding protein (FUS). Among the sporadic cases, the etiology is unknown. However, several environmental risk factors have been associated with ALS, including military service, and occupational exposure to pesticides and metals. Irrespective of the cause, the final common pathway is characterized by motor neuron degeneration leading to muscle atrophy, cognitive impairment, and paralysis, with most patients dying of respiratory failure after about 3 to 5 years of symptom onset. Studies using murine models of ALS have improved our understanding of the pathophysiology of ALS However, many drugs tested in murine models, with the results interpreted as promising, ultimately failed in human ALS trials, emphasizing the need for new models and tools to enable the screening of novel therapeutics to treat ALS. A promising alternative model for ALS therapeutic discovery is the zebrafish. Zebrafish are an established model organism for studying neurodegenerative diseases, including ALS, Parkinson's disease, Huntington's disease, and others. Zebrafish neurobiology has a particularly high degree of evolutionary conservation at the genetic, molecular, cellular, and behavioral levels; concordantly, zebrafish neurodegenerative disease models exhibit the hallmark features of human brain pathology, including protein aggregation, synaptic dysfunction, and loss of neuronal cells. A robust repertoire of stereotypic behavioral phenotypes in zebrafish can be leveraged to assess motor function. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Moreover, these small animals have an economy of scale that is not feasible in other vertebrate systems. Finally, methodological advantages compared to rodent models include the feasibility of real-time, whole- organism imaging via microscopy and their experimental tractability with an established toolbox for chemical and genetic perturbations in high throughput. These features make zebrafish ideally suited to enable neurotherapeutic discovery for ALS. Genetic models of ALS in zebrafish have been generated by targeting sod1, tardbp, c9orf72, and fus. These models recapitulate key features of human ALS including defects including motor neuron axonopathy, abnormal neuromuscular junctions, mitochondrial defects, protein aggregation, muscle degeneration, motor neuron loss, and locomotion deficits. However, many of these zebrafish mutants die at the embryonic or larval stage of development; thus, these early embryonic models do not represent the progressive neurodegeneration that is characteristic of ALS in humans. By contrast, the SOD1G93Azebrafish model used in these Examples is an adult-onset model of ALS. Also, SOD1G93Azebrafish mimic the slower clinical deterioration characteristic of human disease, with phenotypic changes beginning in early adulthood and gradually progressing over months. Importantly, the slower rate of disease progression in the zebrafish SOD1G93Amodel also provides a longer diagnostic and treatment window as compared to that of the SOD1G93Amurine model which spans only about 10 weeks. Another notable strength of this model is that the level of expressed SOD1G93Amutant protein is similar to that observed in ALS patients, in contrast to the extreme supraphysiological levels of mutant protein required to induce the ALS phenotype in some mouse models. Thus, this zebrafish SOD1G93Amodel in combination with EIM assessment creates a particularly clinically relevant platform to model human ALS. The Examples herein illustrate methods and results for advancing zebrafish as an alternative model of ALS with efficient tools to monitor disease progression by combining an adult-onset zebrafish model of SOD1G93AALS with electrophysiological biomarkers to quantitatively assess neuromuscular disease. By employing EIM in ALS clinical trials, it is possible to detect disease progression more rapidly and sensitively, in addition to the effect of therapy. Thus, EIM can serve as a biomarker in both ALS preclinical studies and clinical trials. Example 11: Morphology changes in amyotrophic lateral sclerosis in zebrafish Experimental methods Zebrafish were housed under standard conditions (28.5 °C on a 14 / 10 h light / dark cycle) and fed decapsulated brine shrimp (Artemia) twice a day. The SOD1G93Atransgenic line was outcrossed to the wildtype AB line, i.e., the line it was generated in. Sibling wildtypes were used as controls. In all assays, both males and females were used. Body mass measurements were determined by removing excess water with paper towels and weighing the animal on a tared scale. For protein measurements via Western blot analysis, Euthanized animals were bisected posterior to the dorsal fin and a section of trunk tissue was subsequently lysed in RIPA buffer supplemented with protease inhibitors. Lysates were run on Bis-Tris gels (4%-20%) in MOPS buffer and transferred to PVDF membranes. The antibodies used were SOD1 (Fisher Scientific PIPA130195) and GAPDH (Cell Signaling #2118). For histology staining, animals were euthanized and the trunk was severed with surgical scissors using the anal fin as a morphological landmark. The tissue was fixed in Dietrich’s fixative for several days. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Subsequently, the tissue was paraffin-embedded and sectioned, and slides were H&E stained at the BIDMC Histology Core. To detect spinal cord motor neurons, 18 µm paraffin sections were stained with 0.2% Cresyl Violet (2% acetic acid, 60 mM sodium acetate) overnight. Subsequently, the slides were transferred through the following series: water, differentiation solution (2 drops of acetic acid in 95% ethanol), and 100% ethanol. After dipping in xylene, the slides were mounted in PERMOUNT™ medium. Images were captured on a Keyence BZ-X710 Imaging Platform. Myofibers were analyzed using Keyence BZ-X Analyzer software as previously described. Briefly, to determine the cross-sectional myofiber area, the automated hybrid counting tool was used to segment the myofibers in combination with manual editing with the fine edit tool to correct inaccurate segmentation. Two tissue sections were analyzed per animal. About 400 myofibers per animal were analyzed. Measurements were acquired by two blinded observers. Spinal cord motor neurons were quantified using morphological criteria in Cresyl violet stained tissue sections (18 µm sections). The features used to identify motor neurons included: soma shape, size, and position, and the presence of Nissl bodies. Three sections per animal were analyzed by two blinded observers. Results In this SOD1G93AALS zebrafish model, zebrafish ubiquitously express the human ALS variant SOD1-G93A (FIG.12). The expression of human mutant SOD1-G93A protein is approximately 2-fold greater that of endogenous zebrafish wildtype SOD1 (FIG.12). Pathological changes in the nervous system of SOD1G93Atransgenic zebrafish begin in early adulthood. These defects occur over several months exhibiting a gradual and incremental degeneration that ultimately culminates in motor neuron death (FIG.13). To quantify motor neurons in the spinal cords of SOD1G93Aand wildtype animals, cross-sectional tissue sections were obtained from animals at the vertebra level immediately posterior to the dorsal fin. Subsequently, spinal cord motor neurons were quantified in Cresyl violet stained sections at two time points (FIG.14A-14D). At the 40-week timepoint, there were significantly fewer spinal cord motor neurons in SOD1G93Azebrafish as compared to wildtype animals (17.2 ± 2.9 versus 25.4 ± 3.1 motor neurons, respectively; p<0.0001, n=16, FIG.15). By contrast, at the 20-week time point, which is early in the modeled pathogenesis of the disease (FIG.13), there was no difference in the number of spinal cord motor neurons (FIG.15 and FIGS.16A-16B). These results demonstrate that overexpression of the human ALS variant SOD1G93Ain zebrafish leads to significant loss of motor neurons in the spinal cords of SOD1G93Aanimals, which develops in early adulthood. In addition to the observed loss of spinal cord motor neurons in the SOD1G93Aanimals, the SOD1G93Azebrafish exhibited decreased caudal muscle cross-sectional area of Type 1 and 2 fibers. The decreased weight and trunk thickness observed between the 20- and 40-week time points in SOD1G93Azebrafish can indicate a loss of muscle mass (FIG.17A-17D). To quantify structural changes in skeletal muscle, histological studies and morphometric analyses were performed on 20- and 40-week-old SOD1G93Azebrafish. The architecture of caudal skeletal musculature in 20-week SOD1G93Azebrafish was normal as compared to wildtype zebrafish (FIGS.18A-18E). In contrast, at 40 weeks, the caudal skeletal musculature of SOD1G93Azebrafish exhibited smaller myofibers and increased space between myofibers (FIGS.19A-19D). The mean cross-sectional area of Type 2 fibers was significantly decreased in PATENT ATTORNEY DOCKET NO.: 01948-291WO2 SOD1G93Azebrafish as compared to wildtype zebrafish at the 40-week time point (1161 ± 213 versus 896 ± 203 µm2, n=22-24, p<0.001; FIG.20A), in addition, the distribution of fiber sizes was shifted towards smaller sizes (FIG.20B). The mean cross-sectional area of Type 1 fibers was also significantly decreased in SOD1G93Azebrafish as compared to wildtype zebrafish at the 40-week time point (348 ± 13 versus 222 ± 10 µm2, n=25-26, p<0.0001; FIGS.21A-21D and FIG.22A), in addition, the distribution of fiber sizes was shifted towards smaller sizes (FIG.22B). The observed reduction in myofiber CSA in SOD1G93Azebrafish indicates the development of skeletal muscle atrophy. Example 12: EIM measurements to monitor amyotrophic lateral sclerosis EIM has not been previously used in zebrafish models of ALS. Here we tested the hypothesis that surface electrical impedance myography detects neuromuscular diseases in adult zebrafish with SOD1G93AALS. We studied wildtype and ALS zebrafish at two time points: pre-disease state / early disease state and diseased state and acquired multifrequency electrical impedance data (1-10 kHz) and assessed established metrics of ALS disease, including spinal cord motor neuron density, the cross- sectional area of Type 1 and 2 myofibers, and motoric function (swimming endurance). In ALS zebrafish, as compared to wildtype animals, EIM parameters (i.e., phase angle, reactance, and resistance) at 2 kHz were robust metrics that detected neuromuscular disease. Moreover, these parameters exhibited reproducible measurements in both healthy and ALS zebrafish. In sum, these findings support that EIM is an effective tool to monitor neuromuscular disease progression in adult ALS zebrafish, and the metrics identified here create a fast, noninvasive, and reliable platform that will enable the future efficacy testing of candidate therapeutics that could be used to treat human disease. Experimental methods EIM measurements were acquired from the descaled epaxial caudal musculature of anesthetized zebrafish. The dorsal fin was used as a landmark to position the electrode. The electrode array consisted of four blunt-tip needle electrodes which were connected to the mView impedance-measuring device (MYOLEX®, Inc.). A micromanipulator (World Precision Instruments, Sarasota, FL) and a stereo- dissection microscope were used to control the electrode placement and its angle of contact. A pair of outer electrodes delivered alternating electrical current (400 µA, 41 frequencies between 1 kHz and 1 MHz) to the muscle while the inner pair of inner electrodes measured the resulting voltage. The mView device was connected to a laptop running mView software (MYOLEX®, Inc.) to acquire the data. For reproducibility analyses, the data were analyzed in GraphPad Prism (version 10), RStudio (2023.12.1), and Stata (version 18). Data are presented as the mean ± standard deviation unless otherwise specified. Significance was assessed using Mann–Whitney tests or ANOVAs. ICC estimates were calculated using a single-measurement, absolute-agreement, 2-way mixed-effects model. ICC values less than 0.5 were defined as poor reliability, values between 0.5 and 0.75 were defined as moderate reliability, values between 0.75 and 0.9 were defined as good reliability, and values greater than 0.90 were defined as excellent reliability. To calculate the mean percentage difference the following equation was used: (|test 1 – test 2| ∕ (test 1 + test 2) ∕ 2)) x 100. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Results We conducted electrophysiological assessments on live zebrafish using a noninvasive electrical impedance myography methodology that we recently developed for adult zebrafish. This impedance- based technique enables noninvasive assessment of skeletal muscle health. Multifrequency EIM data from 1 to 1,000 kHz was collected from the dorsal caudal musculature in SOD1G93Aand wildtype animals that were 20 and 40 weeks of age. At 20 weeks of age, there were no overall differences in phase, reactance, and resistance between SOD1G93Azebrafish and wildtype zebrafish (FIGS.23A-23C). At 40 weeks of age, the multifrequency graphs of SOD1G93Azebrafish exhibited a trend of decreased phase, reactance, and resistance at low frequencies (i.e., ≤ 50 kHz), as compared to wildtype animals (FIGS. 23D-23F). These findings indicate that prior to the onset of abnormal innervation (20 weeks of age), the bioelectrical impedance properties of skeletal muscles in SOD1G93Azebrafish were similar to those of wildtypes. By contrast, in diseased animals (40 weeks of age), reduced bioelectrical impedance was observed in the caudal musculature of SOD1G93Azebrafish. Thus, multifrequency EIM noninvasively detected changes in ALS skeletal muscle, as compared to wild-type muscle, that developed as the disease progressed in zebrafish. Collectively, these data demonstrate multifrequency EIM detects the development of ALS in this animal model. Next, we conducted single-frequency analyses of the EIM data at 2 and 50 kHz. At the 20-week time point, there were no significant differences in 2 kHz phase, reactance, and resistance between SOD1G93Aand wildtype animals (FIG.24). In contrast, at the 40-week time point, there were significant reductions in 2 kHz phase, reactance, and resistance (all p<0.0001) in SOD1G93Aanimals as compared to wildtype animals (FIG.25), in which the measured phase was 11.6 ± 3.4 versus 17.4 ± 3.5 degrees, the measured reactance was 331 ± 138 versus 719 ± 249, and the measured resistance was 1591 ± 305 versus 2209 ± 428 in SOD1G93Azebrafish versus wildtype zebrafish, respectively. At 50 kHz in the 20- week time point, there were no significant differences in 50 kHz phase, reactance, and resistance between SOD1G93Aand wildtype animals (FIG.26). At the 40-week time point, there were significant reductions in 50 kHz reactance (p=0.0001) and resistance (all p=0.02) in SOD1G93Aanimals as compared to wildtype animals (FIG.27), in which measured reactance was 488 ± 65 versus 600 ± 94, and the measured resistance was 376 ± 117 versus 469 ± 126, for SOD1G93Azebrafish versus wildtype zebrafish, respectively. Together, these findings indicate that electrical impedance myography robustly detects differences between the skeletal muscle of SOD1G93Aand wildtype animals, especially at 2 kHz. The findings of the electrical impedance myography study are also consistent with the morphological changes in SOD1G93Azebrafish observed in histological studies shown in Example 11. Together, these endpoints provide a method for detecting ALS progression and serve as a platform for determining efficacy of candidate therapeutic agents for the treatment of ALS. To assess the reproducibility of the EIM methodology, multiple measurements were acquired for each animal, in which the animal was removed from the EIM set-up, placed back on the set-up, and an additional measurement for each parameter was recorded at 2 kHz. In healthy animals, the mean percentage difference between the two measurements for phase angle, reactance, and resistance was 7.4 ± 0.9%, 7.9 ± 1.2%, and 4.0 ± 0.4%, respectively (n=22). In ALS animals, the mean percentage difference for phase angle, reactance, and resistance was 10.5 ± 1.4%, 11.7 ± 2.1%, and 6.1 ± 0.9%, respectively (n=22). To further evaluate test-retest reliability, the intraclass correlation coefficient (ICC) PATENT ATTORNEY DOCKET NO.: 01948-291WO2 between test and retest measurements were calculated for each EIM parameter. In healthy animals, the ICC for phase, reactance, and resistance was 0.86, 0.93, and 0.90 (p<0.001), respectively. In ALS animals, the ICC for phase, reactance, and resistance was 0.85, 0.84, and 0.87 (p<0.001), respectively. These data are summarized in Table 4, shown below. SEM: standard error of the mean.†Single-measurement, absolute-agreement, 2-way mixed- effects model.††Bland-Altman analyses. The data described in this Example therefore demonstrate that EIM is a useful, highly reproducible method for detecting ALS progression and could be used to monitor a subject’s response to a candidate treatment for ALS (e.g., a treatment comprising glyoxylate). Example 13: Glyoxylate improves skeletal muscle health in amyotrophic lateral sclerosis In ALS animal models, alterations in NAD+ / NADH have been observed in motor neurons and muscles. Restoring NAD+homeostasis has been shown to slow the progression of ALS in animal and human models; however, there are no FDA-approved drugs for ALS that target this mechanism. Glyoxylate is an endogenous, cell membrane-permeable, intermediary metabolite that can generate both NADH and NAD+because of its oxidized and reduced forms and its activity in both the cytoplasm and mitochondria. Thus, glyoxylate generates cofactors to support ATP production via both glycolysis and oxidative phosphorylation, in addition to providing cofactors for other cellular processes, all of which may improve energy balance in both neurons and skeletal muscle. Experimental methods Animals at 40-weeks of age were treated daily for four weeks. The compound and vehicle control were administered daily for 2 hours by dissolving it in the water that bathes the fish, where it was absorbed through the gill epithelium, skin, and gut. Results As shown in Examples 11 and 12, untreated animals exhibit significant skeletal muscle atrophy and defects in electrophysiology at the 40-week time point. Vehicle or glyoxylate (80 µM) was administered daily to SOD1G93Azebrafish starting at 40 weeks of age for four weeks. Subsequently, EIM was conducted at multiple frequencies ranging from 1 to 1,000 kHz. In glyoxylate treated animals, these PATENT ATTORNEY DOCKET NO.: 01948-291WO2 measurements exhibited an increase in phase, reactance, and resistance across frequencies as compared to vehicle treated animals (FIGS.28A-28C). In single frequency analyses, there were significant improvements in 2 kHz phase, reactance, and resistance (all p<0.0001) in SOD1G93Aanimals treated with glyoxylate as compared to SOD1G93Aanimals treated with the vehicle control (FIGS.29A- 29C), in which the measured phase was 16.2 ± 1.4 degrees versus 13.8 ± 1.7 degrees, the measured reactance was 674 ± 130 versus 446 ± 74, and the measured resistance was 2293 ± 182 versus 1869 ± 254, in animals treated with glyoxylate versus a vehicle control, respectively. These findings demonstrate significant improvement in the skeletal muscle electrophysiology of SOD1G93Atreated with glyoxylate as compared to a vehicle control. Concordantly, skeletal muscle histology of glyoxylate versus vehicle treated animals demonstrated that glyoxylate treatment increased the size of myofibers in the caudal trunk musculature of SOD1G93Aanimals (FIGS.30A-30D). These improvements in skeletal muscle function and morphology, therefore, demonstrate that glyoxylate can be used for treating skeletal muscle atrophy in ALS. Example 14: Treatment of a subject at risk of amyotrophic lateral sclerosis A 40-year old male subject is determined to be at risk of developing familial ALS based on a genetic counseling session and a genetic test (e.g., genetic sequencing data) indicating a mutation in a gene associated with ALS (e.g., C9ORF72, SOD1, TARDBP, or FUS). The subject can be administered glyoxylate treatment to maintain skeletal muscle mass and physical ability as he ages. The subject can self-report their physical strength and abilities during the treatment regimen, and their muscle tissue can be assessed through physical examination and EIM. The subject may have adiposity and measured muscle resistance and reactance parameters consistent with a generally healthy 40-year old male. The subject may receive, for example, 1 to 10 mg / kg glyoxylate (e.g., 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg) by subcutaneous injections once a week to maintain muscle mass and muscle function. At several subsequent doctor’s appointments, the subject’s physician may take EIM measurements and perform physical examinations. The subject’s physician may report an increase in muscle mass and stabilized EIM measurements as compared to the subject’s pre- treatment measurements and, for example, as compared to a 40-year old male at risk of developing familial ALS that did not receive glyoxylate treatment or relative to a control reference or baseline measurement. Example 15: Treatment of a subject with amyotrophic lateral sclerosis A 55-year old male subject is diagnosed with ALS (e.g., sporadic ALS or familial ALS) via electrodiagnostic tests and magnetic resonance imaging (MRI) and can be administered intramuscular injections of glyoxylate twice a week. The subject can be administered a single dose of glyoxylate in an amount of 1 to 10 mg / kg (e.g., 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg). The subject can be assessed for maintained muscle mass, mobility, and muscle strength, for example, via EIM, a grip strength test, and / or an MRI. Maintained values in one or more of these metrics, as compared to an individual with ALS that was not administered glyoxylate treatment, or relative to a control reference or baseline measurement, indicates treatment of ALS. PATENT ATTORNEY DOCKET NO.: 01948-291WO2 Other Embodiments All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each independent publication or patent application was specifically and individually indicated to be incorporated by reference. While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations following, in general, the principles and including such departures from the invention that come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth, and follows in the scope of the claims. Other embodiments are within the claims.

Claims

PATENT ATTORNEY DOCKET NO.: 01948-291WO2 CLAIMS 1. A method of treating progressive skeletal muscle atrophy in a subject comprising administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject.

2. A method of treating cognitive decline in a subject exhibiting progressive skeletal muscle atrophy comprising administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject.

3. A method of treating excess adiposity or obesity in a subject exhibiting progressive skeletal muscle atrophy comprising administering a composition comprising glyoxylate or a pharmaceutically acceptable salt thereof to the subject.

4. The method of any one of claims 1-3, wherein the progressive skeletal muscle atrophy is due to an age-related condition.

5. The method of any one of claims 1-4, wherein the progressive skeletal muscle atrophy is due to cachexia.

6. The method of any one of claims 1-5, wherein the progressive skeletal muscle atrophy is due to sarcopenia.

7. The method of any one of claims 1-6, wherein the progressive skeletal muscle atrophy is due to amyotrophic lateral sclerosis.

8. The method of any one of claims 1-3, wherein the progressive skeletal muscle atrophy is due to a muscular dystrophy or a congenital myopathy.

9. The method of any one of claims 1-8, wherein the progressive skeletal muscle atrophy is due to an underlying immunological or inflammatory illness, a neurodegenerative disease, cellular or mitochondrial dysfunction, a genetic mutation, malnutrition, or diminished physical activity.

10. The method of any one of claims 1-9, wherein the progressive skeletal muscle atrophy is due to idiopathic skeletal muscle atrophy.

11. The method of any one of claims 1-10, wherein the subject is a mammal.

12. The method of claim 11, wherein the mammal is a human.

13. The method of claim 12, wherein the human is younger than 18 years old.

14. The method of claim 12, wherein the human is 18 years old or older.PATENT ATTORNEY DOCKET NO.: 01948-291WO2 15. The method of claim 14, wherein the human is above the age of 40 years old.

16. The method of claim 15, wherein the human is between the ages of 70 and 85 years old.

17. The method of claim 15, wherein the human is above the age of 85 years old.

18. The method of any one of claims 1-17, wherein the subject exhibits or is at risk of loss of skeletal muscle mass or function prior to administration of the composition.

19. The method of any one of claims 1-18, wherein the skeletal muscle mass of the subject is or has been determined by performing electrical impedance myography (EIM), magnetic resonance imaging (MRI), and / or dual-energy X-ray absorptiometry (DXA).

20. The method of any one of claims 1-15, wherein the skeletal muscle function of the subject is or has been determined by performing EIM, a strength assessment of the subject, and / or a mobility assessment of the subject.

21. The method of claim 20, wherein the subject is characterized as having sarcopenia based on at least one criterion from a strength or mobility assessment summarized in Table 1.

22. The method of any one of claims 1-21, wherein, after administration of the composition, the method further comprises monitoring the subject for changes in skeletal muscle mass of the subject relative to an assessment of the subject’s skeletal muscle mass prior to administration of the composition.

23. The method of any one of claims 1-21, wherein the composition is administered at a dose between 1 mg / kg and 10 mg / kg.

24. The method of any one of claims 1-21, wherein the composition is administered at a dose between 35 mg and 900 mg.

25. The method of claim 23 or 24, wherein the dose of the composition is administered one or more times weekly.

26. The method of claim 23 or 24, wherein the dose of the composition is administered daily.

27. The method of any one of claims 1-26, wherein the method comprises administering one or more additional therapies.

28. The method of claim 27, wherein the additional therapy comprises an exercise program and / or a dietary program such as a high-leucine diet or a high-protein diet.PATENT ATTORNEY DOCKET NO.: 01948-291WO2 29. The method of claim 27, wherein the additional therapy comprises administration of β- aminoisobutyric acid, a stereoisomer, or a pharmaceutically acceptable salt form thereof.

30. The method of claim 27, wherein the additional therapy comprises administration of a sirtuin-1 (SIRT1) activator, optionally a cyclobutene or a cyclobutene-scaffold-based molecule.

31. The method of claim 27, wherein the additional therapy comprises administration of an inhibitory nucleic acid that targets C9ORF72, SOD1, TARDBP, FUS, PFN1, NEFH, PRPH, or DCTN1.

32. The method of claim 27, wherein the additional therapy comprises administration of edaravone, dextromethorphan hydrobromide and quinidine sulfate, riluzole, or tofersen.

33. The method of any one of claims 1-32, wherein the composition is administered as a single dose.

34. The method of any one of claims 1-32, wherein the composition is administered in two or more separate doses.

35. The method of any one of claims 1-34, wherein the composition is administered one or more times per day, week, month, or year.

36. The method of any one of claims 1-35, wherein the composition is administered to the subject by oral, intravenous, cutaneous, subcutaneous, intradermal, nasal, pulmonary, intramuscular, or intraperitoneal administration.

37. The method of claim 36, wherein the composition is administered subcutaneously.

38. The method of claim 36, wherein the composition is administered by intramuscular injection.

39. The method of claim 36, wherein the composition is administered by oral administration.

40. The method of any one of claims 36-38, wherein the composition is administered at a volume between 350 μL and 3.5 mL.

41. The method of any one of claims 36-39, wherein the composition has a sustained release formulation.

42. The method of any one of claims 1-41, wherein, after administration of the composition, the subject is characterized as exhibiting an increase in skeletal muscle mass relative to the subject prior to administration of the composition or relative a control subject.PATENT ATTORNEY DOCKET NO.: 01948-291WO2 43. The method of claim 42, wherein the increase in skeletal muscle mass is at least a 10% increase.

44. The method of claim 43, wherein the increase in skeletal muscle mass is between a 15 and 20% increase.

45. The method of any one of claims 1-41, wherein, after administration of the composition, the subject is characterized as exhibiting an increase in skeletal muscle function relative to the subject prior to administration of the composition or relative a control subject.

46. The method of claim 45, wherein the increase in skeletal muscle function is at least a 15% increase.

47. The method of claim 22, wherein the monitoring comprises performing EIM, strength assessment, and / or mobility assessment.

48. The method of claim 47, wherein the method further comprises changing the dose amount, frequency of administration, or term of administration of the composition based on a result of the monitoring.

49. The method of claim 48, wherein the change comprises an increase in the dose amount, frequency of administration, and / or term of administration of the composition.

50. The method of claim 49, wherein the dose is increased by at least 50% relative to a prior dose administered to the subject.

51. The method of claim 49, wherein the frequency of administration is increased by at least one additional time of administration per day, week, month, or year.

52. The method of any one of claims 48-51, wherein the method further comprises monitoring the skeletal muscle mass or skeletal muscle function of the subject after the change.

53. The method of claim 52, wherein the monitoring comprises performing EIM, a strength assessment, and / or a mobility assessment.

54. The method of any one of claims 1-53, wherein the method further comprises measuring a level of a metabolite in a blood sample obtained from the subject.

55. The method of claim 54, wherein the blood sample is whole blood, plasma, and / or serum.

56. The method of claim 54 or 55, wherein the metabolite is a cofactor or byproduct of the citric acid cycle.PATENT ATTORNEY DOCKET NO.: 01948-291WO2 57. The method of any one of claims 54-56, wherein the level of the metabolite is measured prior to administration of the composition.

58. The method of claim 55, wherein the level of the metabolite is measured one or more times during the course of a treatment regimen comprising administration of the composition.

59. The method of any one of claims 54-58, wherein the level of the metabolite indicates changes in skeletal muscle of the subject.

60. The method of any one of claims 54-59, wherein the metabolite is selected from the group consisting of a lipid, a carbohydrate, a glycan, a citric acid cycle intermediate, a bile acid, an amino acid, an organic acid, a purine, and a pyrimidine.

61. The method of claim 60, wherein the metabolite is a reduced or oxidized form of nicotinamide adenine dinucleotide (NAD).

62. The method of any one of claims 1-61, wherein glyoxylate or a pharmaceutically acceptable salt thereof is supplemented or substituted with a composition comprising any one or more of a structurally similar compound selected from glyceraldehyde, glyoxal, pyruvate, oxaloacetate, methylglyoxal, alpha- ketobutyrate, alpha-ketoglutarate, 3-methyl-2-oxovaleric acid, dihydroxyacetone, acetaldehyde, oxalate, glycolate, malate, lactate, or a combination thereof and a pharmaceutically acceptable excipient.

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