Biomarkers for Therapy of FSHD

The Boston Biomedical Research Institute Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center for FSHD was established to further understanding of the underlying molecular and cellular pathology of facioscapulohumeral muscular dystrophy (FSHD) and to establish muscle tissue and cell repository biomarker databases as resources for FSHD research and evaluation of outcomes of FSHD clinical trials.

The Center currently sponsors four (4) multi-investigator research projects and three (3) cores:

Project 1. "Clinical Trials and Biomarkers of Myostatin Inhibition." This project, led by Drs. Kathryn Wagner and Louis Kunkel, partners with Acceleron Pharma in developing biomarkers for the myostatin inhibitor, ACE-031, in healthy human subjects and mice and developing protocols for clinical trials using biomarkers to test the efficacy of myostatin inhibitors in FSHD patients.

Project 2. "Biomarker Discovery in Muscles from FSHD Patients." This project, led by Drs. Louis M. Kunkel, Mayana Zatz, and Robert J. Bloch, undertakes to identify mRNAs, miRNAs and protein biomarkers through gene expression array and proteomics analyses of biopsies of affected and unaffected muscles obtained from FSHD patients and first degree relatives. These studies undertake to define the molecular pathology underlying FSHD and identify disease biomarkers for FSHD clinical trials.

Project 3. "Myogenesis Studies for FSHD Biomarkers." This project, led by Drs. Charles Emerson and Woodring Wright, investigates the growth and differentiation characteristics of mortal and immortalized muscle progenitors derived from muscle biopsies of affected and unaffected muscles obtained from FSHD patients and first degree relatives. These studies undertake to identify cellular defects in myogenic cell lineages from affected FSHD muscles that affect their regenerative capacity and aging as well as to identify disease biomarkers expressed in FSHD muscle progenitor cells and newly differentiated fibers.

Project 4. "Mouse Model Studies for FSHD Biomarkers." This project, led by Drs. Jeffrey B. Miller and Robert J. Bloch, investigates muscle disease pathology and biomarker expression in existing and newly generated mouse models of FSHD to identify validated FSHD mouse models for studies of disease progression and pathology and for therapeutic development.

Core A. An "Administrative Core" provides the administrative and financial structure and fosters a communicative scientific environment within the Center. This Core is the information hub to communicate Center activities to the greater scientific community, governmental (NIH) agencies and foundations, other Wellstone Centers, and the lay and FSHD patient advocate communities. Core A, together with the FSH Society and Mr. Daniel Perez, also will organize scientific, patient and community outreach meetings.

Core B. An "Education and Training Core" oversees a pre- and postdoctoral fellowship program designed to train and mentor young scientists for careers in skeletal muscle and muscular dystrophy research, with a strong focus on training for FSHD research. This Core also organizes an annual Center retreat to enable trainees to present research findings and interact with Center scientists.

Core C. A "Cell Core" will establish a tissue and cell repository of muscle biopsies and immortalized and mortal muscle progenitor cells derived from affected and unaffected muscles of FSHD patients and first degree relatives and establish a FSHD muscle biomarker database from investigations in Projects 1-4. This Core also partners with Genzyme/Myosix to utilize and develop technologies for identification and isolation of muscle cell progenitors from FSHD muscles.  Contents of the cell and tissue repository will be available for for distribution to FSHD researchers for their basic and therapeutic studies.

The Center is seeking collaborations with researchers in the international community to foster research on FSHD, as well as engaging new industrial partners committed to developing therapeutics and undertake clinical trials for treatment of FSHD.