Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center

美国国立卫生研究院参议员Paul B. Wellstone中心是国家努力降低肌肉疾病发病率和死亡率的核心，也是发现和开发更有效的预防、诊断和治疗方法的主要来源。北卡罗来纳大学（UNC）的“目标”是在北卡罗莱纳州建立一个一流的Wellstone中心，该中心已经组建了一个高度互动的研究小组，创建了一个由经验丰富的临床研究人员(dr。鲍尔斯和沃尔夫)，专家基础实验室(博士。Samulski， Xiao和Beecham)和大型动物模型（Kornegay博士）专注于开发，测试和建立治疗杜氏肌营养不良症（DMD）和其他遗传性肌肉疾病的治疗方法。该中心的一个主要主题是将新的基于基因的治疗方法推进到肌肉疾病的临床。这一努力的动力源于这样一个事实，即北卡罗来纳大学基因治疗中心（GTC）近年来取得了重大进展，建立了一个基础，使从实验台到临床的全面发展努力使DMD基因治疗更接近现实（例如GMP载体生产设施，DMD狗模型核心）。本着这一使命的精神，UNC在MDA的支持下，使用新设计的AAV载体（Samulski博士）和迷你肌营养不良蛋白（dys）基因（Xiao博士）独立启动了首个基于基因的DMD治疗。从我们的I期研究中出现的一个共同主题和提案的主要焦点是，建立对基于基因的治疗方法治疗后的安全性和有效性的清晰理解，并将这些努力推进到选定的人类临床试验中，以显示治疗的潜力。与FDA继续讨论最有效和谨慎的方式，以最小的风险和最大的收益推进我们基于基因治疗的DMD患者的努力，这导致了拟议的MDCRC Wellstone中心申请。MDCRC将包括3个项目（项目1 PI-Dr. Powers和Dr. Wolff，项目2 PI-Dr. Wolff）。Xiao，项目3 PI- Samulski博士（项目1-3）和四个核心：一个行政核心(PI- dr。裘德·萨穆斯基（Jude Samulski）训练核心，矢量核心（PI杰弗里·比查姆博士）和大型动物核心（PI- Kornegay博士）。

The NIH Senator Paul B. Wellstone Centers are the centerpiece of the nation's effort to reduce morbidity and mortality from muscular disorders and are a major source of discovery and development of more effective approaches to prevention, diagnosis, and therapy. The University of North Carolina (UNC) "goal" of establishing a premier Wellstone Center in the state of North Carolina has assembled a highly interactive research group creating a dynamic program comprised of experienced clinical investigators (Drs. Powers & Wolff), expert basic laboratories (Drs. Samulski, Xiao, and Beecham), and large animal models (Dr. Kornegay) focused on developing, testing, and establishing therapeutic treatments for Duchenne Muscular Dystrophy (DMD) and other genetic muscle disorders. A major theme of the Center is to advance novel gene based therapies into the clinic for muscle disorders. The impetus for this effort stems from the fact that UNC Gene Therapy Center (GTC) has made significant strides in recent years to build the foundation that will enable development of a full-scale bench-to-bedside effort bringing gene therapy for DMD closer to a reality (e.g. GMP vector production facility, DMD dog model core). In the spirit of this mission, UNC with support from MDA has independently initiated the first gene-based therapy for DMD using a newly engineered AAV vector (Dr. Samulski) and a mini-dystrophin (dys) gene (Dr. Xiao). A common theme emerging from our Phase I studies and a primary focus of the proposal, relates to establishing a clear understanding of safety and efficacy after treatment with gene based therapeutics and advancing these efforts into selected human clinical trials that will show potential for treatment. Continued discussion with FDA for most efficient and prudent manner to advance our gene therapy based efforts to DMD patients with minimum risk and maximum benefit has lead to the proposed MDCRC Wellstone Center application. The MDCRC will consist of 3 projects (Project 1 PI- Dr. Powers coPI Dr. Wolff -, Project 2 PI-Dr. Xiao, Project 3 PI- Dr. Samulski, (Projects 1-3) and four cores: an Administrative core (PI-Dr. Jude Samulski, Co-PI-Dr. Powers) Training Core, Vector Core (PI Dr. Jeffrey Beecham) and Large animal core (PI- Dr. Kornegay).