Development of novel therapies for aging-induced skeletal muscle atrophy.

描述（由申请人提供）：年龄引起的骨骼肌萎缩，也称为肌肉减少症，在美国影响了大约3000万人，通常导致虚弱，生活质量降低，跌倒，骨折，衰弱，胰岛素抵抗，住院时间延长和养老院安置。然而，目前的治疗建议（治疗潜在疾病，改善营养和运动，如果可能的话）往往是可悲的不足。因此，衰老引起的骨骼肌萎缩是一个巨大的未满足的医疗需求和全球市场。Emmyon公司的总体目标是开发一种药物治疗衰老引起的骨骼肌萎缩。在初步研究中，Emmyon在爱荷华大学的创始人在多个小鼠模型中发现了两种抑制骨骼肌萎缩的化合物。这两种化合物都是在可食用植物中发现的天然产物（表明具有良好的安全性），并且这些化合物在小鼠中的强大作用表明它们作为骨骼肌萎缩的药物治疗具有突出的潜力。Emmyon的创始人公布了其中一种化合物熊果酸的数据，引起了制药和食品行业的广泛兴趣。Emmyon的创始人尚未公开披露第二种化合物的身份。基于这项研究，爱荷华大学申请了两种化合物用于治疗衰老性骨骼肌萎缩的使用专利。Emmyon公司正在就该知识产权的独家授权进行最后阶段的谈判。在这项I期SBIR研究中，Emmyon将开始开发熊果酸和第二种化合物作为衰老性骨骼肌萎缩的药物治疗方法。虽然这两种化合物在禁食、肢体固定和肌肉去神经支配期间都能减少骨骼肌萎缩，但它们在衰老诱导的骨骼肌萎缩中的作用尚不清楚。在拟议的研究中，Emmyon将通过对老年小鼠施用熊果酸和第二种化合物来确定熊果酸和第二种化合物作为治疗衰老性骨骼肌萎缩的可行性。复合功效将通过测量握力、骨骼肌质量、骨骼肌纤维大小和分子萎缩介质来确定。该研究还将评估这两种化合物对脂肪量、血糖和脂质水平以及肝肾功能的影响。Emmyon的目标是找出至少一种能减少老年小鼠骨骼肌萎缩的化合物。在II期研究中，Emmyon将开发一种或两种化合物的配方，并进行药代动力学和毒理学研究，随后进行IND申请。根据效力和功效，一种或两种化合物可以构成药物或药用食品的基础。最初的临床研究将面向FDA批准预防和治疗老年人骨骼肌萎缩。

DESCRIPTION (provided by applicant): 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.