Development of Novel Small Molecule Therapies for Skeletal Muscle Atrophy

PROJECT SUMMARYABSTRACT Skeletal muscle atrophy diminishes the health and quality of life of tens of millions of people in the US aloneFrequent causes of muscle atrophywhich often co exist in the same patientinclude agingmalnutritionmuscle disusecritical illnesscertain medicationsand a broad range of chronic illnesses including cancerheart failureCOPDdiabetesrenal failurecirrhosisrheumatoid arthritisand HIV AIDSFrequent effects of muscle atrophy include weaknessimpaired activityfallsprolonged hospitalizationdelayed rehabilitationloss of independent livingand increased mortalityHoweverdespite its broad clinical impactskeletal muscle atrophy lacks a medical therapy and thus represents an enormous unmet medical needA major goal of EmmyonIncis to discover and develop a pharmaceutical for skeletal muscle atrophyIn our Phase I STTR projectwe designed and synthesized a series of novel chemical entitiesNCEswhich were then subjected to primary screening in cultured skeletal myotubesfollowed by secondary investigations in a mouse model of immobilization induced muscle atrophyThrough these studieswe discoveredand subsequently patenteda confidential and proprietary small molecule compoundEMMYthat potently and effectively reduces skeletal muscle atrophy in vivoIn this Phase II SBIR proposalEmmyon seeks to advance the development of EMMYand related molecules as pharmaceuticals for skeletal muscle atrophySpecificallywe will further investigate EMMYandapos s safetyefficacyand mechanisms of action in two distinct and complimentary mouse models of muscle atrophyimmobilization induced and age related muscle atrophytogetherthese studies will significantly advance our understanding of EMMYandif successfulsignificantly advance EMMYtowards final development and commercialization in SBIR Phase IIIIn parallel to those studieswe will design and synthesize a new and expanded series ofadditional NCEswhich will be screened and compared to EMMYin cultured human skeletal myotubes and mouse models of skeletal muscle atrophythrough these studieswe hope to identify additional NCEs with pharmacologic properties that are similar to or perhaps even better than those of EMMYAltogetherthrough these studieswe hope to rigorously advance the scientific understanding and commercial development of a highly promising new class of pharmaceutical agents for skeletal muscle atrophy PROJECT NARRATIVE Skeletal muscle atrophyalso known as muscle wastingis a widespread and serious condition that affects tens of millions of people in the US aloneUnfortunatelyright nowwe do not have any medicines to help prevent or treat skeletal muscle atrophy in patientsTo help address this issuewe propose a Phase II SBIR study to investigate and develop new and promising potential medicines for skeletal muscle atrophy