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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZAR1-KM-J (M1))
Program Officer
Porter, John D
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University of Rochester
Schools of Dentistry
United States
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Hoskins, Jason W; Ofori, Leslie O; Chen, Catherine Z et al. (2014) Lomofungin and dilomofungin: inhibitors of MBNL1-CUG RNA binding with distinct cellular effects. Nucleic Acids Res 42:6591-602
Thornton, Charles A (2014) Myotonic dystrophy. Neurol Clin 32:705-19, viii
Statland, Jeffrey M; Tawil, Rabi (2014) Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve 49:520-7
Batra, Ranjan; Charizanis, Konstantinos; Manchanda, Mini et al. (2014) Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Mol Cell 56:311-22
Heatwole, Chad; Bode, Rita; Johnson, Nicholas et al. (2014) Myotonic Dystrophy Health Index: initial evaluation of a disease-specific outcome measure. Muscle Nerve 49:906-14
Rzuczek, Suzanne G; Gao, Yu; Tang, Zhen-Zhi et al. (2013) Features of modularly assembled compounds that impart bioactivity against an RNA target. ACS Chem Biol 8:2312-21
Hilbert, James E; Ashizawa, Tetsuo; Day, John W et al. (2013) Diagnostic odyssey of patients with myotonic dystrophy. J Neurol 260:2497-504
Childs-Disney, Jessica L; Stepniak-Konieczna, Ewa; Tran, Tuan et al. (2013) Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules. Nat Commun 4:2044
Kalman, Lisa; Tarleton, Jack; Hitch, Monica et al. (2013) Development of a genomic DNA reference material panel for myotonic dystrophy type 1 (DM1) genetic testing. J Mol Diagn 15:518-25
Coonrod, Leslie A; Nakamori, Masayuki; Wang, Wenli et al. (2013) Reducing levels of toxic RNA with small molecules. ACS Chem Biol 8:2528-37

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