Partnering to treat an Orphan Disease Duchenne Muscular Dystrophy

杜氏肌营养不良（DMD）是一种严重致残和致命的疾病。这是最常见的肌肉萎缩症，影响全球1:50 000男孩；然而，它是一种孤儿病，在开发新疗法方面的投资相对较少。因此，这种毁灭性的疾病没有好的治疗方法。在这项申请中，肯尼迪克里格研究所的Kathryn Wagner博士和华盛顿大学的Stanley Froehner博士提议将赛诺菲的一种化合物重新用于治疗杜氏肌营养不良症。在该奖项的UH2部分，Froehner博士将在mdx/utr小鼠模型中测试该化合物的功效，并将监督由CRO进行的少年毒理学研究。在及时向FDA提交IND申请后，全美儿童医院的Wagner博士和Jerry Mendell博士将在有限数量的DMD受试者中进行Ib期SAD和MAD研究，以确定安全性和剂量。在该奖项的UH3部分，DMD男孩的ii期研究将在全国多个地点进行。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，以及持续给药在DMD中是否安全且耐受性良好。鉴于DMD危及生命和致残的性质，预计IIa期临床试验将成为寻求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.