Muscular Dystrophy Cooperative Research Center

肌营养不良症合作研究中心

• 批准号: 7533659
• 负责人: RICHARD T MOXLEY
• 金额: $ 148.26万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7533659
• 关键词: Muscular; Dystrophy; Cooperative; Research; Center

DESCRIPTION (provided by applicant): Major strengths of the University of Rochester Wellstone MDCRC are: 5 years of experience in operating our current Wellstone Center; a large group of highly motivated patients with myotonic dystrophy (DM1) eager to support basic research and participate in clinical studies; enthusiastic investigators with longstanding expertise in DM1; and, a nurturing environment that includes a NIH CTSA and a recently funded Fields Center for FSHD and Neuromuscular Research. These assets will allow us to continue our current Wellstone Center scientific projects in the future without using renewal funds. Our renewal Wellstone Center will use its funds for 2 scientific projects and l scientific resources core and focus on new research projects to establish optimal methods to assess treatment efficacy in DM1 patients and to identify potential new therapies. To evaluate bench to bedside aspects of disease progression, Project 1, "Disease Progression in Myotonic Dystrophy", will undertake: studies of potential causes of somatic instability of the unstable DM1 CTG repeat in clonally derived cell lines; a search for molecular pathophysiologic determinants of mutant DM1 RNA in fine needle muscle biopsy specimens obtained from a cohort of 80 patients with each patient providing samples from a proximal and a distal leg muscle; and, a longitudinal study to identify optimal measures of disease progression (that are clinically significant to patients) by performing serial measurements of strength and function, muscle mass, myotonia, and quality of life in this same cohort of 80 patients at baseline, 12 and 36 months. To identify potential new treatments Project 2, "Experimental Therapy of Myotonic Dystrophy", will perform: a trial of muscle blind gene therapy in 3 mouse models of DM1; identification and characterization of small molecules showing post-transcriptional up-regulation of muscle blind 1 using the screening platform developed by PTC Therapeutics; and, a treatment trial in 2 transgenic mouse models of DM1 using a 25 nt morpholino composed entirely of CAG repeats. The scientific resources core combines our existing Tissue Repository Core and NIH Registry of DM Patients and Family members to provide national resources for research on DM. Projects 1 & 2 contribute to this core. The Training/Education core will train 1 pre- and 1 post-doctoral fellow during years 2-5 and will develop web based educational materials for patients, family members, care providers and researchers.

描述（由申请人提供）：罗切斯特韦尔斯通大学MDCRC的主要优势是：经营我们当前的韦尔斯通中心的5年经验；一大批高度积极的肌发育症患者（DM1）渴望支持基础研究并参与临床研究；在DM1方面拥有长期专业知识的热情调查员；以及一个养育环境，包括NIH CTSA和最近资助的FSHD和神经肌肉研究中心。这些资产将使我们将来继续我们当前的Wellstone Center科学项目，而无需使用续签资金。我们的续签井石中心将使用其资金用于2个科学项目和L科学资源的核心，并专注于新的研究项目，以建立最佳方法来评估DM1患者的治疗疗效并确定潜在的新疗法。为了评估疾病进展的基准方面，项目1，“肌发育不全中的疾病进展”，将进行：对克隆衍生的细胞系中不稳定的DM1 CTG重复重复的躯体不稳定的潜在原因的研究；搜索在细针肌肉活检标本中，从80例患者获得的细针肌活检标本中突变DM1 RNA的分子病理生理决定因素，每位患者提供来自近端和远端腿部肌肉的样品；以及一项纵向研究，旨在通过对80例基线，12和36个月的80名患者进行强度和功能，肌肉质量，肌肉质量，肌肉质量，肌肉质量和生活质量来确定疾病进展的最佳度量（对患者临床意义）。为了确定潜在的新疗法项目2，“肌营养不良症的实验疗法”将进行：在3种DM1小鼠模型中肌肉盲基因治疗的试验；使用PTC疗法开发的筛选平台的小分子的鉴定和表征，显示出肌肉盲1的转录后上调；并且，使用完全由CAG重复序列组成的25 nt吗啡的DM1的两种转基因小鼠模型进行了治疗试验。科学资源核心结合了我们现有的组织存储库核心和DM患者和家人的NIH注册表，以提供有关DM研究的国家资源。项目1和2为此核心做出了贡献。培训/教育核心将在2 - 5年期间培训1个前和1名博士后研究员，并将为患者，家庭成员，护理提供者和研究人员开发基于网络的教育材料。