Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center

The long-term goal of the UF Wellstone Muscular Dystrophy Specialized Center (MDSRC) is to promote the translation of promising emerging therapeutic targets into clinical trials for muscular dystrophy patients. This  Wellstone  MDSRC  is  organized  around  the  central  theme  of  preserving  skeletal  muscle  and  cardiac  muscle function in the muscular dystrophies by delineating disease-­modifying targets and developing therapeutic strategies. We have shown that inhibiting inflammation/fibrosis will improve skeletal muscle repair and limit fibro-­fatty replacement of both skeletal muscle and cardiac muscle. We now are additionally focused on the metabolic aspects of the muscular dystrophies, as well as the impact of calcium handling dysfunction in both cardiac and skeletal muscles, and the development of therapeutics to address these problems. Project 1 (Drs.  Sweeney  and  Hammers)  will  evaluate  anti-­inflammatory  and  anti-­fibrotic  drugs  in  the  course  of  delineating the short-­comings of AAV-­µdystrophin gene therapy, and developing therapies to improve its effectiveness. Preliminary data suggests that the hearts of dystrophin-­deficient animals will not be rescued by µdystrophin  gene  therapy  unless  additional  means  of  addressing  calcium  dysfunction  in  the  heart  can  be  developed. In Project 2, Drs. McNally and Spencer will examine the effects of intermittent steroid dosing on the inflammatory infiltrate in muscle, determining how metabolic programming alters this process and how this is reflected in blood biomarkers. Together, they will also investigate a novel agent directed at promoting CaMKII activation. This project takes advantage of Dr. Spencer’s expertise in profiling immune cells in muscle and will also use human materials collected from the Weekly Steroids in Muscular Dystrophy (WSiMD, NCT04054375) trial. In Project 3, Drs. Walter and Vandenborne will continue to develop non-­invasive biomarkers for following disease progression as well as conduct human studies that complement the mouse studies of Projects 1 and 2. Our Physiological Assessment Core (Core C: Shared Scientific Resource Core), under the direction of Dr. Barton, will support Projects 1 and 2, as well as continue as a national resource for evaluating therapeutic interventions in mouse models of muscular dystrophy. This Center has a major training and educational component (Core B: Training Core), under the direction of Drs. Andrew Judge (UF) and Rachelle Crosbie (UCLA).

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