Facioscapulohumeral muscular dystrophy (FSHD) is a disorder that often renders persons unable to walk by early adulthood. FSHD is a genetic neuromuscular disease marked by its progressive skeletal muscle weakness due to the death of muscle cells and tissue. This slowly progressive muscle disorder affects about 1 in 20,000 persons. The clinical course varies among people, but about 80% eventually lose the ability to walk. In the U.S. and Europe, more than 30,000 persons are living with FSHD.
FSHD arises due to a mutation in a repetitive stretch of DNA. The causative mutation is a contraction in this repetitive DNA that permits the expression of a gene, DUX4, that is silent in unaffected individuals. DUX4 is toxic to muscle cells and its expression leads to muscle cell death.
To address this pathogenic gene activation, Fulcrum is developing a small molecule that stabilizes the disease process through the restoration of the repressive DUX4 gene regulation.
While there are steps that patients can take to minimize complications from FSHD, there are currently no known treatments that will reverse the muscle weakness and wasting in FSHD.