Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) have multisystem complications that are serious, progressive, and often disabling. Recent advances in understanding the mechanisms of DM have guided the development of experimental therapies. There is now renewed urgency to enhance the translational resources that are needed to facilitate current and future clinical trials. To help achieve these goals, we propose to sustain and enhance the resources of the oldest and most comprehensive Registry for patients with myotonic dystrophy type 1 (DM1), type 2 (DM2), and FSHD. The main goals of the Registry are to assist researchers in the recruitment of patients for clinical studies and trials, to develop an extensive database of longitudinal patient information, and to promote community outreach with patients and family members to increase awareness, communication, and participation in the research process. In parallel, to help researchers understand what matters most to patients. Overall, the Registry has functioned effectively up to now, but we are proposing several changes to make it more effective in the future. First, we will begin the process of incorporating genetic diagnosis into Registry participation, with the goal of providing genetic confirmation for FSHD patients who do not presently have it (approximately half of FSHD Registry members). Second, we will establish capability for online data collection, using methods that protect patient confidentiality. Third, we will establish telemedicine links with a group of Registry participants, for targeted data collection at a distance. This will expand opportunities for patients anywhere to take part in studies, and improve the quality and scope of data in the Registry. As a corollary, we will examine validity of data collected through telemedicine study visits. Another goal of our Shared Resource Core is to improve access to key models of DM1 and DM2, through distribution of mouse models that are useful for preclinical drug development, in a way that minimizes lead-time for performing drug-discovery experiments. Overall, the Shared Resource Core will be serve the needs of researchers in our Center, the larger community of investigators who study autosomal dominant forms of muscular dystrophy, and the patients and families who live with these disorders.
| Sznajder, ?ukasz J; Thomas, James D; Carrell, Ellie M et al. (2018) Intron retention induced by microsatellite expansions as a disease biomarker. Proc Natl Acad Sci U S A 115:4234-4239 |
| Pinto, Belinda S; Saxena, Tanvi; Oliveira, Ruan et al. (2017) Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9. Mol Cell 68:479-490.e5 |
