Major strengths of the University of Rochester Wellstone MDCRC are: 5 years of experience in operating our current Wellstone Center;a large group of highly motivated patients with myotonic dystrophy (DM1) eager to support basic research and participate in clinical studies;enthusiastic investigators with longstanding expertise in DM1;and, a nurturing environment that includes a NIH CTSA and a recently funded Fields Center for FSHD and Neuromuscular Research. These assets will allow us to continue our current Wellstone Center scientific projects in the future without using renewal funds. Our renewal Wellstone Center will use its funds for 2 scientific projects and l scientific resources core and focus on new research projects to establish optimal methods to assess treatment efficacy in DM1 patients and to identify potential new therapies. To evaluate bench to bedside aspects of disease progression, Project 1, """"""""Disease Progression in Myotonic Dystrophy"""""""", will undertake: studies of potential causes of somatic instability of the unstable DM1 CTG repeat in clonally derived cell lines;a search for molecular pathophysiologic determinants of mutant DM1 RNA in fine needle muscle biopsy specimens obtained from a cohort of 80 patients with each patient providing samples from a proximal and a distal leg muscle;and, a longitudinal study to identify optimal measures of disease progression (that are clinically significant to patients) by performing serial measurements of strength and function, muscle mass, myotonia, and quality of life in this same cohort of 80 patients at baseline, 12 and 36 months. To identify potential new treatments Project 2, """"""""Experimental Therapy of Myotonic Dystrophy"""""""", will perform: a trial of muscle blind gene therapy in 3 mouse models of DM1;identification and characterization of small molecules showing post-transcriptional up-regulation of muscle blind 1 using the screening platform developed by PTC Therapeutics;and, a treatment trial in 2 transgenic mouse models of DM1 using a 25 nt morpholino composed entirely of CAG repeats. The scientific resources core combines our existing Tissue Repository Core and NIH Registry of DM Patients and Family members to provide national resources for research on DM. Projects 1 &2 contribute to this core. The Training/Education core will train 1 pre- and 1 post-doctoral fellow during years 2-5 and will develop web based educational materials for patients, family members, care providers and researchers.
Showing the most recent 10 out of 88 publications
