MANGANESE ENHANCED MRI: NON-INVASIVE MEASURE OF PATHOGENESIS OF DYSTROPHINOPATHY

Baylor College Of Medicine, Houston TX

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Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Duchenne muscular dystrophy (DMD) is the most devastating type of muscular dystrophy, with an incidence of 1 in every 3500 males. DMD is an X-linked, muscle-wasting disease caused by mutations in the cytoskeletal protein dystrophin.. Young DMD patients experience muscle damage that is followed by regeneration; however, as the disease progresses regeneration is impeded and muscle fibers are progressively replaced by connective tissue and fatty deposits. Profound muscle weakness results in decreased mobility by 10 to 12 year of age and eventually death by the age of 20 to 30 due to respiratory and/or cardiac failure. While there is currently no treatment for the disease, many different therapeutic approaches for DMD are entering clinical trials. Based on the trajectory of the pathogenic phenotype precise and reliable non-invasive measures that follow the temporal progression of the dystrophic process in children are needed., The goal of this proposal is to develop and validate a novel MRI technique (manganese enhanced MRI, MEMRI) as a noninvasive imaging procedure to assess skeletal muscle function in muscular dystrophy. The Specific Aims of the proposed research are to: 1) establish the biodistribution of Mn2+ within skeletal muscle after intravenous injection, and 2) establish a robust method using MEMRI for assessment of structural/functional changes in dystrophic skeletal muscle. If successful, the proposed research will provide a robust non- invasive method currently not employed for assessing both structure and function of skeletal muscle in DMD, which will be critical in evaluating the beneficial effects of these therapies.