Discovery of Novel Pharmaceutical Agents for Skeletal Muscle Atrophy

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PROJECT SUMMARY / ABSTRACT 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.