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: 10261494
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261494
• 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; 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; diet-induced obesity; dietary; 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.

项目总结/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（通常在同一患者中共存）包括衰老，营养不良， 肌肉废用，危重病，某些药物，以及广泛的慢性疾病，包括癌症， 心力衰竭、COPD、糖尿病、肾衰竭、肝硬化、类风湿性关节炎和HIV/AIDS。频繁的影响 肌肉萎缩包括虚弱、活动受损、福尔斯、住院时间延长、康复延迟、丧失 独立生活和死亡率上升。然而，尽管其广泛的临床影响，骨骼肌， 萎缩缺乏药物治疗，因此代表了巨大的未满足的医疗需求。一个主要目标 关于Emmyon，Inc.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，我们发现了一种机密和专有的小分子化合物（EMMY 1- 06)这显著增加了力量和肌肉质量，并显著减少了固定引起的 肌肉萎缩此外，我们发现EMMY 1 -06对骨骼肌的有益作用伴随着 通过显著减少脂肪量，从而进一步预防肥胖和肥胖相关的葡萄糖 不容忍在第二阶段SBIR提案中，我们寻求通过推进 开发EMMY 1 -06和相关分子作为治疗骨骼肌萎缩的药物， 相关代谢紊乱。具体而言，我们将进一步研究EMMY 1 -06的安全性，有效性， 在骨骼肌萎缩和饮食诱导的肥胖和葡萄糖小鼠模型中的作用机制 这些研究将共同显著推进EMMY 1 -06的最终开发， SBIR第三阶段的商业化。在我们详细研究EMMY 1 -06的同时，我们将设计， 合成和表征结构上与EMMY 1 -06相关新化合物， 具有类似于或可能甚至优于本发明的那些药理学性质的其它化合物， Emmy1-06总之，这些研究将严格推进科学理解和商业 开发了一种非常有前途的新型骨骼肌萎缩症药物。