Aging-induced skeletal muscle atrophy, also known as sarcopenia, affects approximately 30 million people in the United States, often leading to weakness, reduced quality-of-life, falls, fractures, debilitation, insulin resistance, prolonged hospitalizations and nursing home placement. However, current treatment recommendations (treatment of underlying illness, improved nutrition and exercise if possible) are often woefully inadequate. Thus, aging-induced skeletal muscle atrophy represents an enormous unmet medical need and market worldwide. The overall goal of Emmyon, Inc. is to develop a pharmacologic therapy for aging-induced skeletal muscle atrophy. In preliminary studies, Emmyon's founders at the University of Iowa discovered two compounds that inhibit skeletal muscle atrophy in multiple mouse models. Both compounds are natural products found in edible plants (suggesting a favorable safety profile) and the robust effects of these compounds in mice suggest outstanding potential as pharmacologic therapies for skeletal muscle atrophy. Data from one of the compounds, ursolic acid, has been published by Emmyon's founders, leading to widespread interest from the pharmaceutical and food industries. Emmyon's founders have not yet publically disclosed the identity of the second compound. Based on this research, the University of Iowa applied for use patents for both compounds in the treatment of aging-induced skeletal muscle atrophy. Emmyon, Inc. is in the final stages of negotiation for an exclusive license to this intellectual property. In this phase I SBIR study, Emmyon will begin to develop ursolic acid and the second compound as pharmacologic therapies for aging-induced skeletal muscle atrophy. Although both compounds reduce skeletal muscle atrophy during fasting, limb immobilization and muscle denervation, their effects in aging-induced skeletal muscle atrophy are not yet known. In the proposed studies, Emmyon will determine the feasibility of ursolic acid and the second compound as therapies for aging-induced skeletal muscle atrophy by administering both compounds to aged mice. Compound efficacy will be determined by measuring grip strength, skeletal muscle mass, skeletal muscle fiber size and molecular atrophy mediators. The study will also assess the effects of both compounds on fat mass, blood glucose and lipid levels, and liver and kidney function. Emmyon's goal is to identify at least one compound that reduces skeletal muscle atrophy in aged mice. In Phase II studies, Emmyon will develop formulations of one or both compounds and carry them to pharmacokinetic and toxicology studies, followed by IND application(s). Depending on potency and efficacy, one or both compounds could form the basis for pharmaceuticals or medicinal foods. Initial clinical studies will be geared towards FDA approval for the prevention and treatment of skeletal muscle atrophy in the elderly.
In elderly patients, skeletal muscle wasting is a common and serious problem, but lacks a medical therapy. A long-term goal of Emmyon, Inc. is to develop medicines that prevent muscle wasting in elderly patients. In this phase I study, Emmyon will test whether two proprietary chemical compounds reduce muscle wasting in aged mice. If so, these compounds will be developed for aging humans in phase II studies.
| Moro, Tatiana; Ebert, Scott M; Adams, Christopher M et al. (2016) Amino Acid Sensing in Skeletal Muscle. Trends Endocrinol Metab 27:796-806 |
| Ebert, Scott M; Dyle, Michael C; Bullard, Steven A et al. (2015) Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. J Biol Chem 290:25497-511 |
| Adams, Christopher M; Ebert, Scott M; Dyle, Michael C (2015) Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy. Curr Opin Clin Nutr Metab Care 18:263-8 |
