Muscular Dystrophy Cooperative Research Center

 描述（由申请人提供）：爱荷华州大学MDCRC的总体目标是对由肌营养不良蛋白异常加工引起的各种肌营养不良症（肌营养不良蛋白病）进行临床前和临床转化研究。该中心将通过对肌营养不良症的转化研究和提供先进的诊断服务来实现这一总体目标。我们的MDCRC应用程序由两个项目和三个核心组成，所有这些项目都由在基础，转化和临床研究方面具有卓越和合作记录的研究人员指导。项目1（坎贝尔）将研究肌营养不良聚糖病的分子发病机制，并使用已知突变的肌营养不良聚糖病患者的细胞，评价导致肌营养不良聚糖糖基化异常的各种机制缺陷。这个项目的一个主要资产是我们最近开发的几个dystroglycanopathy基因的酶测定。项目2（马修斯）将识别和表征所有基因型的肌营养不良聚糖病患者，并定义可用于在治疗试验期间评估定义队列中疾病进展的结局指标。候选修饰基因和血清生物标志物也将在不同的患者人群中建立和评价。核心A（坎贝尔和摩尔）是一个行政核心，将协调中心内外的活动， 作为一种手段，以促进互动和协作的研究环境，并参与肌肉萎缩症的研究患者。核心B（摩尔），一个肌肉组织/细胞培养/诊断核心，将支持项目1和2，作为国家组织和细胞培养资源的研究，提供专门的诊断测试范围广泛的肌营养不良症，并保持所需的基础设施，在临床试验期间评估肌肉活检。最后，核心C（马修斯和坎贝尔）将协调我们的培训和教育计划。该中心提供的支持包括每年为两名医科学生提供奖学金，使他们能够在该中心进行研究，并与马修斯博士一起参与病人的护理。该中心高度整合的核心和项目，加上与国内和国际领导人在肌营养不良症领域的广泛合作，将加快临床前转化研究的发现克里思，并建立一个肌营养不良症患者队列的临床试验准备。

 DESCRIPTION (provided by applicant): The overall goal of the University of Iowa MDCRC is to perform pre-clinical and clinical translational research on the various muscular dystrophies that arise from abnormal processing of the dystroglycan protein (dystroglycanopathies). The Center will achieve this overall goal by enabling translational research on the dystroglycanopathies, and providing advanced diagnostic services. Our MDCRC application is composed of two projects and three cores, all of which are directed by investigators with a proven track record of excellence and collaboration in basic, translational and clinical research. Project 1 (Campbell) will investigate the molecular pathogenesis of the dystroglycanopathies and evaluate various mechanistic defects that lead to abnormalities in dystroglycan glycosylation, using cells from dystroglycanopathy patients with known mutations. A major asset for this project is our recently developed enzymatic assays for several dystroglycanopathy genes. Project 2 (Mathews) will identify and characterize dystroglycanopathy patients of all genotypes, and define outcome measures that can be used to evaluate disease progression in defined cohorts during therapeutic trials. Candidate modifier genes and serum biomarkers will also be established and evaluated in different patient populations. Core A (Campbell and Moore) is an administrative core that will coordinate the activities within and outside the Center, as a means to promote an interactive and collaborative research environment, and to engage patients in muscular dystrophy research. Core B (Moore), a Muscle-Tissue/Cell-Culture/Diagnostics Core, will support Projects 1 and 2, serve as a national tissue and cell-culture resource for research, provide specialized diagnostic testing for a wide range of muscular dystrophies, and maintain the infrastructure needed for the evaluation of muscle biopsies during clinical trials. Finally, Core C (Mathews and Campbell) will coordinate our Training and Education initiative. Among the support this Core provides will be fellowships enabling two medical students per year to perform research in the Center and to participate in the care of patients alongside Dr. Mathews. The highly integrated cores and projects of this Center, coupled with extensive collaborations with national and international leaders in the field of dystroglycanopathies, will accelerate the tempo of discovery in preclinical translational research, and also establish the clinical-trial readiness of a cohort of dystroglycanopathy patients.