Project II: Muscular Dystrophy Cooperative Research Center

项目2摘要 糖代谢不良症是一种表型和遗传异质性的子集 由α-肌营养不良聚糖的低糖基化引起的肌营养不良症。整体而言 该项目的目标是改善对糖代谢障碍患者的护理。目前， 对这些患者没有特定的治疗方法，治疗主要是对症处理。 我们预计治疗试验将在不久的将来启动。在这个项目中，我们将 通过三个目标努力改善护理。首先，我们将扩展现有的知识 关于影响疾病进展的疾病表现和变量 历史研究。数据收集将包括对运动强度、功能、 言语和语言，以及生活质量。我们将测试潜在的基因变异(SNPs) 在杜氏肌营养不良症中发现，看看他们是否改变了疾病的严重程度 我们的糖尿病营养不良症患者。第二，我们将优化临床结果衡量标准 临床试验所必需的。从我们的纵向研究中收集的临床结果数据是 对试验设计至关重要，并增加了侧重于上肢的新措施 将允许广泛的受试者参与未来的试验。我们还将开发和 测试远程参与模块，将差旅负担和成本降至最低 参与者。最后，我们将识别和验证生物标记物(肌肉超声、血浆 和尿蛋白、血浆和尿microRNAs)对疾病阶段和 使用最先进的检测方法的进展。候选生物标志物将是 使用在自然病史研究中收集的患者结局测量数据进行验证。作为一名 建议的工作结果是，患有糖代谢不良症的患者将得到更好的临床治疗 关注现在和未来，因为我们使用收集的数据来设计测试小说的试验 干预措施。

Project 2 abstract The dystroglycanopathies are a phenotypically and genetically heterogeneous subset of muscular dystrophies caused by hypoglycosylation of alpha-dystroglycan. The overall goal of this project is to improve care of patients with dystroglycanopathies. At present, there is no specific treatment for these patients and management is largely symptomatic. We anticipate that treatment trials will be initiated in the near future. In this project we will work toward improved care through three aims. First, we will extend current knowledge about disease manifestations and variables that impact progression through a natural history study. Data collection will include standard measures of motor strength, function, speech and language, and quality of life. We will test potential gene variants (SNPs) that were identified in Duchenne muscular dystrophy to see if they modify disease severity in our dystroglycanopathy cohort. Second, we will optimize clinical outcome measures required for clinical trials. Clinical outcome data gathered from our longitudinal study is critical for trial design, and the addition of new measures focusing on the upper extremity will allow a wide range of subjects to participate in future trials. We will also develop and test a remote participation module to minimize the travel burden and cost for participants. Finally, we will identify and validate biomarkers (muscle ultrasound, plasma and urine proteins, plasma and urine microRNAs) responsive to disease stage and progression using state-of-the-art detection methods. Candidate biomarkers will be validated using patient outcome measure data collected in the natural history study. As a result of the work proposed, patients with a dystroglycanopathy will receive better clinical care now and in the future as we use the data collected to design trials that test novel interventions.