Muscular Dystrophy Cooperative Research Center

罗彻斯特大学Wellstone MDCRC的主要优势是：5年的Wellstone中心运营经验；一大群积极参与基础研究和临床研究的强直性肌营养不良（DM1）患者；具有DM1长期专业知识的热情调查员；还有一个培育环境，包括NIH CTSA和最近资助的FSHD和神经肌肉研究菲尔兹中心。这些资产将使我们能够在未来继续我们目前的Wellstone中心科学项目，而无需使用更新资金。我们的更新Wellstone中心将利用其2个科学项目和1个科学资源的资金，并将重点放在新的研究项目上，以建立最佳方法来评估DM1患者的治疗效果，并确定潜在的新疗法。为了评估从实验室到临床的疾病进展，项目1“肌强直性营养不良的疾病进展”将进行：研究克隆来源细胞系中不稳定DM1 CTG重复体不稳定的潜在原因；从80名患者的队列中获得的细针肌肉活检标本中寻找突变DM1 RNA的分子病理生理决定因素，每位患者提供近端和远端腿部肌肉的样本；同时，一项纵向研究通过对80名患者在基线、12个月和36个月的力量和功能、肌肉质量、肌强直和生活质量进行系列测量，确定疾病进展的最佳测量方法（对患者具有临床意义）。项目二“肌强直性营养不良的实验治疗”将在3只DM1小鼠模型中进行肌盲基因治疗试验；使用PTC Therapeutics开发的筛选平台鉴定和表征显示肌肉盲1转录后上调的小分子；以及在2只DM1转基因小鼠模型中使用完全由CAG重复序列组成的25 nt morpholino的治疗试验。科学资源核心结合了我们现有的组织库核心和美国国立卫生研究院糖尿病患者和家庭成员登记处，为糖尿病研究提供国家资源。项目1和2为该核心做出贡献。培训/教育核心将在第2-5年培训1名博士前研究员和1名博士后研究员，并将为患者、家属、护理提供者和研究人员开发基于网络的教育材料。

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.