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MDA’s Search for Treatments & Cures

Researchers supported by MDA have contributed to a better understanding of the molecular basis of FSHD, and they’re now applying what’s been learned to the search for treatments.

In 1990, the genetic defect that underlies the disease was located on chromosome 4. Many investigators assumed that one gene would be found that, when flawed, would lead to the development of the symptoms recognized clinically as FSHD.

Mutations in the dystrophin gene on the X chromosome had recently been discovered to underlie Duchenne and Becker muscular dystrophies, and it was believed that FSHD genetics would be similar.

This, however, wasn’t to be the case. No genes were found in the region of chromosome 4 which is known to be shortened in people with FSHD. Instead, the shortened strip of DNA is found in a part of the chromosome where there are no genes. The function of this type of DNA is the subject of scrutiny by research teams around the world.

Recent findings suggest that the flawed DNA on chromosome 4 may play an important role in telling the cell which genes should be processed into proteins and which shouldn’t. All cells have genes that are “turned on” (available to be processed for protein production) and others that are “turned off” (not available for processing). This gene regulation is what distinguishes one type of cell from another — for example, a muscle cell from a bone cell.

In 2002, MDA-funded scientists found that the shortened DNA segment on chromosome 4 may eliminate a site where a molecular braking system normally “lands” and keeps certain genes from being inappropriately turned on.

Reinstating this braking system or using some other method to block the erroneously activated genes or the proteins made from them seems a likely pathway for the eventual treatment of FSHD.

However, other scientists have posed alternative explanations for FSHD. The shortened stretch of DNA on chromosome 4 may, they say, change the shape of the chromosome and affect its interactions with distant genes or with an envelope that surrounds each cell nucleus.