Partnering to treat an Orphan Disease Duchenne Muscular Dystrophy

Duchenne肌营养不良症(DMD)是一种严重致残性和致命性疾病。它是最常见的肌肉营养不良症，全世界有1：5000的男孩受到影响；然而，它是一种孤儿疾病，在开发新疗法方面得到的投资相对较少。因此，对于这种毁灭性的疾病，没有很好的治疗方法。在这份申请中，肯尼迪·克里格研究所的凯瑟琳·瓦格纳博士和华盛顿大学的斯坦利·弗罗纳博士提议将赛诺菲的一种化合物重新用于杜兴肌营养不良。在该奖项的UH2部分，弗罗纳博士将在DMD的MDX/UTR小鼠模型上测试该化合物的疗效，并将监督CRO进行的青少年毒理学研究。在及时向FDA提交IND文件后，国家儿童医院的瓦格纳博士和曾傑瑞·门德尔博士将在有限数量的DMD受试者中进行Ib期SAD和MAD安全性和剂量发现研究。在该奖项的UH3部分，将在全国多个地点对DMD男孩进行IIa阶段研究。所有地点的研究人员都有活跃的DMD诊所和DMD临床试验经验。IIa期研究将确定该化合物是否能改善DMD的功能，以及DMD患者持续给药是否安全和耐受性良好。鉴于DMD具有危及生命和致残的性质，预计IIa期将成为寻求FDA临时批准的关键临床试验。

Duchenne muscular dystrophy (DMD) is a severely disabling and fatal disorder. It is the most common muscular dystrophy, affecting 1:5000 boys worldwide; however, it is an orphan disease which has received relatively little investment toward the development of novel therapeutics. Consequently, there are no good treatments for this devastating disorder. In this application, Dr. Kathryn Wagner from the Kennedy Krieger Institute and Dr. Stanley Froehner from the University of Washington propose to repurpose a Sanofi compound for Duchenne muscular dystrophy. In the UH2 portion of the award, Dr. Froehner will test efficacy of the compound in the mdx/utr mouse model of DMD and will oversee juvenile toxicology studies performed by a CRO. Following timely IND filing with the FDA, Dr. Wagner and Dr. Jerry Mendell at Nationwide Children's Hospital will conduct Phase Ib SAD and MAD studies for safety and dose finding in a limited number of DMD subjects. In the UH3 portion of the award, Phase IIa studies in DMD boys will be conducted at multiple sites across the country. Investigators at all sites have active DMD clinics and experience in DMD clinical trials. The Phase IIa study will determine if the compound results in functional improvement in DMD as well as whether sustained administration is safe and well tolerated in DMD. Given the life threatening and disabling nature of DMD, the Phase IIa is anticipated to be the pivotal clinical trial for seeking provisional FDA approval.