Progress Update: Platform development and candidate drug screening for FSHD

PI: Daniel G. Miller MD PhD

Dan Miller
Dan Miller

The Miller Lab has made exciting progress in the development of a platform for screening genes and compounds with activities that affect FSHD-specific pathogenic processes. This platform (developed using funds provided by The Friends of FSH Research and largely orchestrated by FSHD-Research Scholar Dr. Gregory Block) allows muscle cells to be cultured for long periods of time. Most cells when cultured outside of the body have a limited number of cell divisions before they simply stop dividing, however when expression of the CDK4 and Telomerase genes are “forced” in these cells, they continue to divide as if they had just been removed from someone’s muscle, a finding initially published by FSHD-researcher Dr. Gillian Butler-Browne. The improved longevity growth allow for careful study of a number of different characteristics in the same cells, and removes some of the experimental variability that is seen when comparing cells that have been allowed to divide for different lengths of time. Most significantly, we have optimized conditions that reveal FSHD-specific differences when cells from FSHD-affected individuals are compared to un-affected control individuals. While this may seem obvious, FSHD researchers have been plagued by the somewhat normal growth, differentiation, and lifespan of FSHD muscle cells, and the lack of physical differences in these cells when their growth characteristics are compared to cells derived from biopsies of normal muscles. Putting these two findings together has allowed us to begin to efficiently search for genes and molecules that specifically prevent FSHD-cells from becoming sick. We are excited about the prospects for identification of drug targets that may be useful for developing treatments that slow or eliminate the muscle loss in FSHD.

See original Summary of research proposal.

See year two 2012 grant for continuing research. The new funds will help Dan Miller expand his work and screen compounds which may have an impact on DUX4 production, and therefore on affected muscle.