SBIR-STTR Award

Skeletal Muscle Atrophy is a highly prevalent condition caused by advanced age, Muscle disuse, chronic illness, critical illness, and malnutrition. In addition to being very common, Muscle Atrophy has serious consequences, including weakness, reduced activity and quality of life, falls, fractures, extended hospitalizatio and rehabilitation, nursing home placement, and increased mortality in chronic disease patients and the elderly. However, despite its broad clinical impact, Muscle Atrophy lacks a medical therapy, and current therapeutic approaches (physical rehabilitation, nutritional optimization, and treatment of underlying disease) are often ineffective and/or unfeasible. Thus, Skeletal Muscle Atrophy represents an enormous unmet medical need. A major goal of Emmyon, Inc. is to develop a medical therapy for Skeletal Muscle Atrophy. In our preliminary studies, we discovered ursolic acid (UA) as a Novel small molecule inhibitor of Skeletal Muscle Atrophy. A natural compound found in apple peel and other edible plant materials, UA possesses a favorable safety profile and improves Muscle function in both mice and humans. However, UA has limited potential as a Pharmaceutical because composition-of-matter claims (which are critical for Pharmaceutical development) are not possible for natural compounds. Thus, to translate UA into a medicine, Emmyon initiated a Medicinal Chemistry program to discover UA derivatives that enable composition-of-matter claims and also possess improved pharmacologic characteristics relative to native UA. Through these efforts, Emmyon has generated and tested a series of UA derivatives and discovered two Novel derivatives (EMMY1-05 and EMMY1-06) that significantly increase Muscle strength when administered orally to young adult mice that lack Muscle Atrophy. Furthermore, our data suggest that EMMY1-05 and EMMY1-06 may be more potent than native UA. In this phase I SBIR study, Emmyon will determine if EMMY1-05 and EMMY1-06 reduce Muscle Atrophy. In the proposed studies, we will determine the feasibility of EMMY1-05 and EMMY1-06 as therapies for Muscle Atrophy induced by two distinct causes: limb immobilization and aging. EMMY1-05 and EMMY1-06 will orally administered to mice with immobilization-induced Muscle Atrophy and mice with age-related Muscle Atrophy (sarcopenia). Both UA derivatives will be directly compared to native UA, which is known to reduce Muscle Atrophy following limb immobilization and during aging. Compound efficacy will be determined by assessing grip strength, specific force, Muscle mass, Muscle fiber size, and molecular Atrophy mediators. Our goal is to identify at least one UA derivative that reduces Muscle Atrophy in both mouse models. In Phase II studies, Emmyon will carry the most promising UA derivative forward into pharmacokinetic and toxicology studies in rats and dogs, and then an IND application. Depending on the results of these studies, the initial clinical study would be geared towards FDA approval for the treatment of disuse Muscle Atrophy and/or age-related Muscle Atrophy.

Public Health Relevance Statement:


Public Health Relevance:
Skeletal Muscle Atrophy is a widespread and serious medical problem, but lacks a medical therapy. In this phase I SBIR study, Emmyon, Inc. will generate new chemical compounds and test them in mice to determine if these compounds reduce Muscle Atrophy. Effective compounds will represent promising potential medicines for Skeletal Muscle Atrophy, and will be carried towards human patients in phase II studies.

Skeletal muscle atrophy diminishes the health and quality of life of tens of millions of people in the US alone. Frequent causes of muscle atrophy (which often co-exist in the same patient) include aging, malnutrition, muscle disuse, critical illness, certain medications, and a broad range of chronic illnesses including cancer, heart failure, COPD, diabetes, renal failure, cirrhosis, rheumatoid arthritis, and HIV/AIDS. Frequent effects of muscle atrophy include weakness, impaired activity, falls, prolonged hospitalization, delayed rehabilitation, loss of independent living, and increased mortality. However, despite its broad clinical impact, skeletal muscle atrophy lacks a pharmacologic therapy and thus represents an enormous unmet medical need. A major goal of Emmyon, Inc. is to discover and develop a pharmaceutical for skeletal muscle atrophy. In our Phase I SBIR project, we discovered and patented a confidential and proprietary small molecule compound (EMMY1- 06) that significantly increases strength and muscle mass and significantly reduces immobilization-induced muscle atrophy. In addition, we found that EMMY1-06’s beneficial effects on skeletal muscle are accompanied by striking reductions in fat mass, resulting in additional protection against obesity and obesity-related glucose intolerance. In this Phase II SBIR proposal, we seek to continue this exciting work by advancing the development of EMMY1-06 and related molecules as pharmaceuticals for skeletal muscle atrophy and related metabolic disorders. Specifically, we will further investigate EMMY1-06's safety, efficacy, and mechanisms of action in mouse models of skeletal muscle atrophy and diet-induced obesity and glucose intolerance; together, these studies will significantly advance EMMY1-06 towards final development and commercialization in SBIR Phase III. In parallel to our detailed studies of EMMY1-06, we will design, synthesize and characterize novel compounds that are structurally related to EMMY1-06, seeking to identify additional compounds with pharmacologic properties that are similar to or perhaps even better than those of EMMY1-06. Together, these studies will rigorously advance the scientific understanding and commercial development of a highly promising new class of pharmaceutical agents for skeletal muscle atrophy.

Public Health Relevance Statement:
PROJECT NARRATIVE Skeletal muscle atrophy, also known as muscle wasting, is a widespread and serious condition that affects tens of millions of people in the US alone. Unfortunately, right now, we do not have any medicines to help prevent or treat skeletal muscle atrophy in patients. To help address this issue, we propose a Phase II SBIR study to investigate and develop a new and promising class of potential medicines for skeletal muscle atrophy.

Project Terms:
Address; Advanced Development; Affect; age related; Aging; AIDS/HIV problem; Apple; Atrophic; base; Biological; Cell model; Chemistry; Chronic Disease; Chronic Obstructive Airway Disease; Cirrhosis; Clinical; Clinical Research; commercialization; Critical Illness; Cultured Cells; design; Development; Diabetes Mellitus; Diet; endurance exercise; exercise capacity; falls; Fasting; Fatigue; Fatty acid glycerol esters; FDA approved; Fracture; Fruit; Glucose Intolerance; Goals; Health; Heart failure; Herb; Hospitalization; Human; Immobilization; Impairment; improved; Independent Living; Investigation; Kidney Failure; Lead; Legal patent; Malignant Neoplasms; Malnutrition; Medical; Medicine; Metabolic Diseases; Metabolism; mortality; mouse model; mRNA Expression; Mus; Muscle; muscle form; Muscular Atrophy; Non-Insulin-Dependent Diabetes Mellitus; novel; Obesity; Oral; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; phase 1 study; prevent; programs; Property; Quality of life; Rehabilitation therapy; Rheumatoid Arthritis; Safety; Scientific Advances and Accomplishments; Series; Skeletal Muscle; skeletal muscle wasting; Small Business Innovation Research Grant; small molecule; Structure; Structure-Activity Relationship; Testing; Therapeutic Agents; ursolic acid; Work