Discovery of Novel Pharmaceutical Agents for Skeletal Muscle Atrophy

治疗骨骼肌萎缩的新型药物的发现

• 批准号: 10078386
• 负责人: Christopher M Adams
• 金额: $ 74.54万
• 依托单位: EMMYON, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078386
• 关键词: AIDS/HIV problem; Address; Advanced Development; Affect; Aging; Apple; Atrophic; Biological; Cell model; Chemistry; Chronic Disease; Chronic Obstructive Airway Disease; Cirrhosis; Clinical; Clinical Research; Critical Illness; Cultured Cells; Development; Diabetes Mellitus; Diet; FDA approved; Fasting; Fatigue; Fatty acid glycerol esters; Fracture; Fruit; Glucose Intolerance; Goals; Health; Heart failure; Herb; Hospitalization; Human; Immobilization; Impairment; Independent Living; Investigation; Kidney Failure; Lead; Legal patent; Malignant Neoplasms; Malnutrition; Medical; Medicine; Metabolic Diseases; Metabolism; Mus; Muscle; Muscular Atrophy; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Property; Quality of life; Rehabilitation therapy; Rheumatoid Arthritis; Safety; Scientific Advances and Accomplishments; Series; Skeletal Muscle; Small Business Innovation Research Grant; Structure; Structure-Activity Relationship; Testing; Therapeutic Agents; Work; age related; base; commercialization; design; endurance exercise; exercise capacity; falls; improved; mRNA Expression; mortality; mouse model; muscle form; novel; phase 1 study; prevent; programs; skeletal muscle wasting; small molecule; ursolic acid

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.

项目概要/摘要 仅在美国，骨骼肌萎缩就降低了数千万人的健康和生活质量。 肌肉萎缩的常见原因（通常同时存在于同一患者身上）包括衰老、营养不良、 肌肉废用、危重疾病、某些药物以及包括癌症在内的各种慢性疾病， 心力衰竭、慢性阻塞性肺病、糖尿病、肾衰竭、肝硬化、类风湿性关节炎和艾滋病毒/艾滋病。频繁影响 肌肉萎缩包括无力、活动受损、跌倒、长期住院、康复延迟、丧失 独立生活能力下降，死亡率增加。然而，尽管骨骼肌具有广泛的临床影响， 萎缩缺乏药物治疗，因此代表着巨大的未满足的医疗需求。一个主要目标 Emmyon, Inc. 的目标是发现和开发一种治疗骨骼肌萎缩的药物。在我们的阶段 在 SBIR 项目中，我们发现了一种保密且专有的小分子化合物（EMMY1- 06）显着增加力量和肌肉质量，并显着减少固定引起的 肌肉萎缩。此外，我们发现 EMMY1-06 对骨骼肌的有益作用还伴随着 通过显着减少脂肪量，从而进一步预防肥胖和肥胖相关的葡萄糖 不宽容。在第二阶段 SBIR 提案中，我们寻求通过推进 开发 EMMY1-06 及相关分子作为治疗骨骼肌萎缩和 相关的代谢紊乱。具体来说，我们将进一步研究EMMY1-06的安全性、有效性和 骨骼肌萎缩和饮食诱导的肥胖和葡萄糖小鼠模型的作用机制 不宽容；这些研究将共同​​显着推动 EMMY1-06 走向最终开发和 SBIR III 期商业化。在我们对 EMMY1-06 进行详细研究的同时，我们将设计， 合成并表征与 EMMY1-06 结构相关的新化合物，寻求鉴定 具有与以下药物相似或什至更好的药理学特性的其他化合物 艾美奖 1-06。这些研究将共同​​推动科学理解和商业化 开发一种非常有前途的新型骨骼肌萎缩药物。