Sen Paul D. Wellstone Muscular Dystrophy Cooperative Research Center: Seattle

参议员 Paul D. Wellstone 肌营养不良症合作研究中心：西雅图

基本信息

批准号：
8846541
负责人：
JEFFREY S CHAMBERLAIN
金额：
$ 157.41万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-07 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8846541
关键词：
Address Advanced Development Animal Model Area Basic Science Biological Markers Blood Vessels Canis familiaris Capsid Proteins Catchment Area Cell Line Characteristics Clinical Clinical Research Clinical Trials Code Collaborations Communication Communities Consult Development Disease Dose Duchenne muscular dystrophy Dystrophin Event Facioscapulohumeral Facioscapulohumeral Muscular Dystrophy Foundations Fred Hutchinson Cancer Research Center Funding Future Gene Delivery Gene Transfer Genes Goals Health Heart Human Immune Immune response Individual Inherited Lead Lentivirus Vector Link Magnetic Resonance Imaging Measurement Mediating Medical center Mentors Messenger RNA Methods Modeling Molecular Mus Muscle Muscular Dystrophies Neurologist Patients Pediatric Hospitals Proteins RNA Interference Reagent Regimen Research Research Ethics Research Infrastructure Research Personnel Research Support Resources Respiratory Diaphragm Scientist Serotyping Skeletal Muscle Surrogate Endpoint System Testing Therapeutic Therapeutic Clinical Trial Therapeutic Trials Training Universities Washington Work adeno-associated viral vector base clinical infrastructure data management design gene therapy member micro-dystrophin mouse model outreach outreach program preclinical study programs radiologist safety testing scale up therapy development vector

项目摘要

DESCRIPTION (provided by applicant): This Wellstone application is focused on preclinical and clinical studies of Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD), the two most common forms of dystrophy. This is a collaborative venture between scientists and clinicians at the University of Washington, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital and The University of Rochester. Project 1 focuses on adapting methods for AAV-mediated gene transfer to large animal models for DMD by focusing on expression cassette design, AAV serotypes, physical delivery methods and scale-up to test the hypothesis that AAV vectors expressing microdystrophin can be used to treat all the major muscle groups involved in DMD. In parallel, we will adapt AAV systems for targeting the dominant disorder FSHD by delivering RNAi cassettes to cell lines and mouse models followed by safety testing in dogs. Thus, we are performing preclinical studies to develop clinical trials for dominant and recessively inherited dystrophies by modeling DMD and FSHD. This latter work provides a link to project 2, which will leverage the collaborative research programs on FSHD in Seattle and Rochester for studies of advanced biomarker assessments of disease, and to explore immune mediated events in FSHD. The clinical infrastructure to be developed in Project 2 will lay a foundation for future clinical trials of gen therapy for DMD, FSHD and other MDs at the University of Washington. These studies will be supported by three Cores. An Administrative Core to facilitate communication and coordination between the components of the Center and for overseeing data management and distribution. A Scientific Research Resource Core to provide stocks of AAV and lentiviral vectors to members of the Center and to muscular dystrophy researchers worldwide. This Core will also provide training, consulting and reagents related to muscular dystrophy research and gene transfer. Lastly, an Investigator Development and Patient Outreach Core (IDPO) for a mentored research program in basic and clinical research, and ethics that will prepare new investigators to address the critical needs of individuals with dystrophy. The IDPO will also provide outreach programs to the public and patient communities.

描述（由申请人提供）：这种井石应用集中于杜钦肌营养不良症（DMD）和Facioscapulohumeral肌肉营养不良（FSHD）的临床前和临床研究，这是两种最常见的营养不良形式。这是华盛顿大学，弗雷德·哈钦森癌症研究中心，西雅图儿童医院和罗切斯特大学的科学家与临床医生之间的合作企业。项目1通过专注于表达盒式设计，AAV血清型，物理递送方法和扩大规模来测试表达AAV载体的AAV载体，即表达微育蛋白的AAV载体可用于处理所有涉及DMD参与DMD的主要肌肉组，从而将AAV介导的基因转移到大型动物模型的适应方法转移到大型动物模型中。同时，我们将通过向细胞系和小鼠模型传递RNAi盒，然后在狗中进行安全测试，以适应AAV系统来靶向主导障碍FSHD。因此，我们正在进行临床前研究，以通过对DMD和FSHD进行建模来开发临床试验，以占主导地位和隐性遗传性营养不良。后一项工作提供了与项目2的链接，该链接将利用西雅图和罗切斯特FSHD的合作研究计划进行研究，以研究疾病的先进生物标志物评估，并探索FSHD中的免疫介导的事件。在项目2中开发的临床基础设施将为华盛顿大学的DMD，FSHD和其他MDS的Gen Therapy的未来临床试验奠定基础。这些研究将得到三个核心的支持。一种行政核心，可促进中心组成部分之间的沟通和协调，并监督数据管理和分发。科学的研究资源核心，可为中心成员以及全球肌肉营养不良的研究人员提供AAV和慢病毒载体的库存。该核心还将提供与肌肉营养不良研究和基因转移有关的培训，咨询和试剂。最后，针对基础研究和临床研究的指导研究计划的研究者开发和患者外展核心（IDPO）以及将为新研究人员做好准备以满足营养不良患者的关键需求的道德规范。 IDPO还将向公众和患者社区提供外展计划。