Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral Muscular Dystrophy (FSHD) is one of the most common forms of muscular dystrophy, with onset typically in teens and young adults. FSHD occurs in approximately one in every 20,000 individuals (between 16,000 to 38,000 people) in the United States. There is no cure for FSHD and there are no therapies to treat the underlying cause of FSHD. FSHD causes progressive and asymmetric skeletal muscle loss. Individuals with FSHD typically first show symptoms of weakness in muscles in the face, shoulders, arms and trunk which then progresses to weakness in muscles and in the lower body. This results in physical limitations throughout the whole body, including an inability to lift arms for more than a few seconds, loss of ability to show facial expressions and serious speech impediments. These symptoms cause many people affected by FSHD to become dependent on the use of a wheelchair for mobility.

FSHD is an autosomal dominant genetic disease, meaning a single copy of the disease-associated gene is enough to cause the disease. Individuals with FSHD therefore have a 50-50 chance of passing it from parent to child. It is caused by the abnormal expression of DUX4 (double homeobox 4), a gene involved in embryonic development but not typically expressed in adults. This abnormal expression of DUX4 leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function.

Current treatment approaches are focused on support for activities of daily living and mobility, improved functioning and lowering the risk of complications. They include physical therapy, exercise, pain management and orthopedic interventions.

FSHD Disease Process:

We are developing our AOC FSHD program to treat the underlying cause of FSHD which is the abnormal expression of an embryonic gene, double homeobox 4 or DUX4. Our AOC is designed to reduce the expression of the DUX4 mRNA and the DUX4 protein. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the degenerative processes in FSHD. We are currently working toward initiating clinical studies for our AOC FSHD program in 2022.