Project II: Muscular Dystrophy Cooperative Research Center

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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.