Biomarkers for Therapy of FSHD (U54)

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DESCRIPTION (provided by applicant): A multi-center team proposes to establish a Wellstone Cooperating Research Center focused on identifying biomarkers to evaluate outcomes of clinical trials for facioscapulohumeral muscular dystrophy (FSHD). In Project 1, Dr. K. Wagner (Johns Hopkins Med Sen) will lead a Phase I clinical trial with Acceleron to assess the effects of its myostatin inhibitor, ACE-031, on healthy human subjects, preparatory to assessing its use in FSHD. In Project 2, Drs. L.M. Kunkel (Harvard Med Sch), M. Zatz (U Sao Paolo), and R.J. Bloch (U Maryland Sch Med) will use biopsy samples to identify changes in RNAs and proteins in FSHD, with the aims of identifying additional disease biomarkers and learning how they are altered in healthy human muscle upon myostatin blockade. Project 3, led by Drs. C.P. Emerson Jr. (Boston Biomedical Research Institute: BBRI) and W. Wright (U Texas Southwestern Medical Center), will derive primary and immortal myogenic cell lines from FSHD and normal biopsies to identify biomarkers and examine their role in proliferation, differentiation, and pathogenesis of muscle cells. Project 4, led by Dr. J.B. Miller (BBRI) in collaboration with Dr. Bloch, will use mouse models and cultured human cells to analyze FSHD biomarkers and identify disease mechanisms. The Cell and Tissue Core (Core C) will work with collaborating physicians to collect and curate muscle biopsies from FSHD patients and healthy volunteers. The Core will also be an international resource to maintain and distribute FSHD and normal myogenic cell lines developed in the Center. An Administrative Core (Core A) led by Dr. Emerson will organize regular meetings among the project scientists and will work with Mr. D. Perez (The FSH Society) for community outreach and to organize an annual open scientific meeting on FSHD. Core A will coordinate this activity with the Education and Training Core (Core B), led by Dr. Bloch, which will support two trainees/yr and will organize an annual Center retreat. The Center's research, core, and training activities are thus aimed at identifying and testing FSHD biomarkers for development of new therapies, providing novel reagents for FSHD researchers worldwide, assessing myostatin inhibitors as a potential FSHD therapeutic, and structuring an outstanding environment for training young scientists. Relevance to Public Health. The proposed Wellstone Center will identify biomarkers for FSHD that can be used for evaluating outcomes in clinical trials.