Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center

美国国立卫生研究院参议员保罗·B·威尔斯通中心是美国减少肌肉疾病发病率和死亡率的中心，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)在北卡罗来纳州建立首屈一指的韦尔斯通中心的“目标”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(Power&Wolff博士)、专家基础实验室(Samulski、肖和Beecham博士)以及大型动物模型(Koreneray博士)组成的动态计划，致力于开发、测试和建立杜氏肌营养不良症(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推动基于基因的新疗法进入肌肉疾病的临床。这一努力的动力来自于这样一个事实，即北卡罗来纳大学基因治疗中心(GTC)近年来在建立基础方面取得了重大进展，这将使全面的工作台到床边工作的开发成为可能，使DMD的基因治疗更接近现实(例如，GMP载体生产设施、DMD犬模型核心)。本着这一使命，北卡罗来纳大学在MDA的支持下，利用新设计的AAV载体(Samulski博士)和微型抗肌营养不良蛋白(Dys)基因(肖博士)，独立启动了第一个基于基因的DMD治疗。从我们的第一阶段研究中出现的一个共同主题，也是该提案的一个主要重点，涉及建立对以基因为基础的疗法治疗后的安全性和有效性的明确理解，并将这些努力推进到将显示治疗潜力的选定的人类临床试验中。与FDA继续讨论以最有效和谨慎的方式将我们基于基因治疗的努力推进到DMD患者的最低风险和最大益处的过程中，导致了MDCRC Wellstone Center的拟议应用。MDCRC将由3个项目组成(项目1 PI-Dr.Power Copi Dr.Wolff-，项目2 PI-Dr。肖，项目3PI-博士萨穆尔斯基(项目1-3)和四个核心：一个行政核心(PI-博士)。朱德·萨穆尔斯基，联合派-博士。能力)训练核心、向量核心(Pi Jeffrey Beecham博士)和大型动物核心(Pi-Dr.Koreneray)。

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).