Dr. Dan G. Miller
Dr. Stephen J. Tapscott
FSHD research continues to move forward with the generous help from the Friends of FSH Research. Dr Dan Miller at the University of Washington’s Institute for Stem Cell and Regenerative Medicine, and Dr. Stephen Tapscott at the Fred Hutchinson Cancer Research Center think that one possible cause of muscle weakness in FSHD is a defect in the generation of muscle tissue that may start before birth, and persist as muscles are continually modified and repaired throughout life. The theory suggests that as cellular reserves become depleted, symptoms of muscle weakness become more prominent. Thus, studying the process of muscle development as cells change from precursor stem cells to muscle may be an important strategy to emphasize differences when comparing cells from FSHD affected and unaffected individuals. Identifying these differences at the cellular level is the key to understanding the disease process, and developing therapeutic strategies.
Until recently, it has been difficult to detect any differences in the behavior of muscle cells from people affected with FSHD. However, recently Dr. Miller and members of his lab have created stem cells from the skin of patients with FSHD. These “induced pluripotent stem (IPS) cells” have the potential to form nearly any cell type in the body, including skeletal muscle. Dr. Miller and his lab have shown that these cells can form such diverse tissues as nerve, bone, cartilage, intestine and muscle. Thus IPS cells are a valuable model system for studying developmentally regulated switches in gene expression that may not be functioning normally during muscle development in FSHD affected individuals.
Dr. Miller and members of the Institute for Stem Cell and Regenerative Medicine at the University of Washington’s South Lake Union campus have begun to encourage these stem cells to form muscle precursors in the laboratory. The objective is to compare gene expression in differentiating cells that were made from individuals with FSHD to similar cells made from the skin of unaffected individuals. Using this model system, Drs Miller and Tapscott hope to unravel key differences in the regulation of gene expression that may be instrumental for the development of FSHD symptoms.
Understanding the FSHD disease process at the cellular level will help define and validate therapeutic targets that might be manipulated to prevent or ameliorate FSHD symptoms. One obvious possibility would be to correct the genetic defect in stem cells from FSHD patients and transplant muscle cells made from these corrected cells back to the injured muscles of the donor. Another possibility is that as therapeutic targets are discovered existing drugs may be identified that would help prevent disease progression, or the search for new drugs can be focused on the disrupted processes. While development of therapeutic strategies for combating FSHD symptoms is a slow and sometimes frustrating process, we are certainly moving closer to this goal as we learn more about the molecular defect in cells from individuals affected by FSHD.