Another approach to improving the health of patients with neuromuscular diseases is to treat the life-threatening effects of the diseases, most notably the muscle degeneration that destroys patients’ ability to walk and ultimately takes their lives. In neuromuscular disorders a protein called myostatin is prematurely activated; in turn, muscle differentiation and muscle growth are suppressed.
One of the most promising approaches the Muscle Group has explored is the use of follistatin to block the myostatin pathway in neuromuscular disorder models. Follistatin is a naturally occurring protein that is present in nearly all human tissue and inhibits myostatin. “Follistatin has emerged as a powerful antagonist of myostatin that can increase muscle mass and strength,” said Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy and Muscle Group member.
Using a virus that infects humans but is not associated with disease (adeno-associated virus) as a vehicle for gene transfer, the Muscle Group has shown that a single injection of a specific type of follistatin into the quadriceps muscle results in increased muscle size and strength in multiple pre-clinical models.
“Our studies indicate that this relatively non-invasive approach could have long-term effects, involve few risks and could potentially be effective in various types of degenerative muscle disorders,” said Dr. Kaspar. It also may be applicable to forms of muscular dystrophy, such as facioscapulohumeral muscular dystrophy, in which gene replacement or other types of gene manipulation are not feasible because of the absence of a specific gene defect.
Dr. Kaspar says that treatment to increase muscle size and strength has never been closer to testing in patients. “We have developed a plan with the Food and Drug Administration and are in the process of performing formal toxicology and biodistribution studies to support initiating a human clinical trial using follistatin,” he said.