Center of Research Translation in Muscular Dystrophy Therapeutic Development

整体CORT 摘要 全国儿童医院研究所基因治疗中心 (RINCH)有一个专门的翻译计划，目标是肌肉营养不良症， 特别是长期以来对为最常见的形式开发有意义的疗法的兴趣， 包括Duchenne肌营养不良症(DMD)和面肩肱骨肌营养不良症 (FSHD)。我们中心的目标包括解开疾病的发病机制和开发新的 治疗范例可以从长凳转换到床边，然后在这个 CORT提议，我们寻求加快这一翻译进程。项目1(PI，Paul Martin， PHD)寻求将目前正在进行DMD试验的一种治疗方法扩展到其他形式的肌营养不良症， 通过应用Galgt2的过表达，一种改变骨骼肌糖基化的酶 促进改善疾病的蛋白质的表达。项目2(PI、Scott Harper、博士) 探索调节DUX4基因表达的新方法以治疗相对 常见且使人衰弱的FSHD。项目3(PI，Kevin Flanigan，MD)寻求快速翻译一个 新发现的肌营养不良蛋白翻译控制机制成为有意义的治疗 患有DMD的男孩。这三个项目都利用了两个关键的研究核心：治疗性病毒 向量设计和开发研究核心(PI，Louise Rodino-Klayac，PhD)和 肌肉营养不良细胞和血清银行核心(Pi，Kim McBride，医学博士)。除 由项目代表的调查人员，拟议的CORT代表了一块更大的肌肉 全国儿童和俄亥俄州立大学的疾病研究基地，为此 介绍了成熟的中试和可行性方案。这一建议的CORT是一致的 NIAMS的使命是找到治疗和治疗癌症的有效方法 改善衰弱形式肌肉疾病患者的生活质量。

Overall CORT Abstract The Center for Gene Therapy at The Research Institute of Nationwide Children's Hospital (RINCH) has a dedicated translational program that targets the muscular dystrophies, with a particular longstanding interest in developing meaningful therapies for the most common forms, including Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Our Center's goals include unraveling disease pathogenesis and developing new treatment paradigms that can be translated from the bench to the bedside, and under this CORT proposal we seek to accelerate this translational process. Project 1 (PI, Paul Martin, PhD) seeks extend a therapy now entering trials in DMD to other forms of muscular dystrophy, by applying the overexpression of Galgt2, an enzyme that alters skeletal muscle glycosylation to boost the expression of proteins that ameliorate disease. Project 2 (PI, Scott Harper, PhD) explores novel approaches to modulating the expression of the DUX4 gene to treat the relatively common and debilitating FSHD. Project 3 (PI, Kevin Flanigan, MD) seeks to rapidly translate a newly discovered mechanism for dystrophin translational control into meaningful therapy for boys with DMD. All three projects make use of two critical research cores: the Therapeutic Viral Vector Design and Development Research Core (PI, Louise Rodino-Klapac, PhD) and the Muscular Dystrophy Cell and Serum Banking Core (PI, Kim McBride, MD). In addition to the investigators represented here by projects, the proposed CORT represents a larger muscle disease research base at the Nationwide Children's and the Ohio State University, for which a well-developed pilot and feasibility program is described. This proposed CORT is consistent with the mission of NIAMS, which has the goal of finding effective treatments for and to improving the quality of life of patients with debilitating forms of muscle disease.