Center of Research Translation in Muscular Dystrophy Therapeutic Development

总体CORT 摘要 国立儿童医院研究所基因治疗中心 （RINCH）有一个专门的翻译计划，目标是肌营养不良症， 特别是对开发针对最常见形式的有意义的疗法的长期兴趣， 包括杜氏肌营养不良症（DMD）和面肩肱肌营养不良症 （FSHD）。我们中心的目标包括揭示疾病的发病机制和开发新的 治疗范例，可以从板凳翻译到床边，并在此 CORT建议我们寻求加速这一转化过程。项目1（PI，Paul Martin， 博士）寻求将一种目前正在DMD中进行试验的疗法扩展到其他形式的肌营养不良症， 通过过度表达Galgt 2，一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哈珀，PhD） 探索新的方法来调节DUX 4基因的表达，以治疗相对 常见且使人衰弱的FSHD。项目3（PI，Kevin Flanigan，MD）旨在快速翻译 新发现的肌营养不良蛋白的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 载体设计和开发研究核心（PI，Louise Rodino-Klapac，博士）和 肌营养不良细胞和血清库核心（PI，Kim McBride，MD）。除了有 研究人员在这里代表的项目，拟议的CORT代表了一个更大的肌肉 国家儿童和俄亥俄州州立大学的疾病研究基地， 良好的试点和可行性方案进行了说明。这个建议的CORT是一致的 NIAMS的使命是寻找有效的治疗方法， 改善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.