Muscular Dystrophy Specialized Research Center

总体总结 爱荷华大学韦尔斯通肌肉营养不良专科研究中心的总体目标 (MDSRC)是对各种肌肉营养不良症进行研究，这些肌营养不良症是由于对 营养不良葡聚糖蛋白(营养不良糖犬病)。该中心将通过开展基础工作来实现这一总体目标 以及在糖代谢不良患者、患者衍生的生物样本和小鼠模型中的翻译研究。我们的 MDSRC申请由两个项目和三个核心组成，所有这些项目都是由调查人员指导的 在基础研究、翻译研究和临床研究方面的卓越表现和协作方面的良好记录。项目1 (Campbell)将通过以下方式研究糖尿病营养不良症的细胞和分子机制 α-DG基质多糖长度与其层粘连蛋白结合关系的研究 对照和糖营养不良症患者成纤维细胞和肌肉活检的性质。更多的研究将 确定由蛋白质-蛋白质和蛋白质-糖调节的马立糖合成的需要 互动。将利用糖营养不良症小鼠模型来确定新的病理生理机制。 并确定改善肌肉功能所需的结构和层粘连蛋白结合特性。项目2 (Mathews)将完善FKRP相关的血糖营养不良症的自然历史， 通过扩大评估患者的临床地点的数量和通过扩展 对临床严重程度较高的患者进行自然病史研究。非FKRP的延长随访 基因分型将确定具有相似运动进展速度的队列，这些队列可能会一起在 基因非特异性临床试验。血液或尿液中的候选蛋白质组生物标志物的全谱 将验证血糖营养不良症的基因类型，并将其与疾病状态相关。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，作为促进 一个互动和协作的研究环境，并让患者参与肌营养不良症的研究。 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研究资源，为各种疾病提供专门的诊断测试 肌肉营养不良，并维护评估肌肉活检所需的基础设施，以支持临床 审判。最后，核心C(马修斯和坎贝尔)将协调我们的培训举措。在这一支持中， 核心提供的奖学金将使每年两名医学生能够在该中心进行研究 与马修斯医生一起参与患者的护理，并有基础科学培训的机会 提供给博士后研究员和本科生研究员。高度集成的核心和 该中心的项目将加快临床前翻译研究的发现速度，还 建立一组糖代谢不良患者的临床试验准备情况。

OVERALL SUMMARY The overall goal of the University of Iowa Wellstone Muscular Dystrophy Specialized Research Center (MDSRC) is to perform research on the various muscular dystrophies that arise from abnormal processing of the dystroglycan protein (dystroglycanopathies). The Center will achieve this overall goal by conducting basic and translational research in dystroglycanopathy patients, patient-derived biosamples, and mouse models. Our MDSRC 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 cellular and molecular mechanisms that underly dystroglycanopathies by evaluating the relationship between α-dystroglycan (α-DG) matriglycan length and its laminin-binding properties in control and dystroglycanopathy patient fibroblasts and muscle biopsies. Additional studies will define the requirements for matriglycan synthesis as regulated by protein-protein and protein-sugar interactions. A dystroglycanopathy mouse model will be utilized to identify novel pathophysiologic mechanisms and determine the structure and laminin binding properties required to improve muscle function. Project 2 (Mathews) will refine the natural history of FKRP-related dystroglycanopathy derived from an established, unique cohort of patients by expanding the number of clinical sites evaluating patients and by extending the natural history study to patients with more advanced clinical severity. Extended follow up of non-FKRP genotypes will identify cohorts that share similar rates of motor progression who might be studied together in gene non-specific clinical trials. Candidate proteomic biomarkers in blood or urine for the full spectrum of dystroglycanopathy genotypes will be validated and related to disease status. 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 to evaluate muscle biopsies in support of clinical trials. Finally, Core C (Mathews and Campbell) will coordinate our Training initiatives. 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, with basic science training opportunities also provided to a postdoctoral fellow and an undergraduate research fellow. The highly integrated cores and projects of this Center will accelerate the tempo of discovery in preclinical translational research, and also establish the clinical-trial readiness of a cohort of dystroglycanopathy patients.