Restoring muscle strength to patients with muscular dystrophy

Muscle cells are some of our most fragile, and damaging them causes injury. For patients with muscular dystrophy, their muscle cells are in a chronic state of disrepair. By targeting a genetic modifier of the disease, Dr. Alexis Demonbreun is developing promising therapies that may reverse the effect and restore muscle strength back to patients. View Halo Profile >>

Tell us about your research…

I am interested in using genetic signals to drive drug development. Working with models of muscular dystrophy, we identified genetic modifiers that change the disease course. For example, we found the genes encoding Latent TGFB binding protein 4 (Ltbp4) and annexin A6 (Anxa6) as promising modifiers of muscular dystrophy and I have been dedicated to using this genetic information to develop novel therapies for muscular dystrophy. In muscular dystrophy, LTBP4 regulates TGFB bioavailability and fibrosis. Annexin A6 orchestrates muscle membrane repair. Our team is developing anti-LTBP4 and pro-annexin A6 biologics with the goals of reducing scar and promoting repair.

Working with models of muscular dystrophy, we identified genetic modifiers that change the disease course.

Can you explain that to a non-scientist?

All tissues, including muscle, require a quick and efficient process of repair. Muscle cells are elongated and with muscle contraction, muscle fibers are unusually susceptible to injury. Some genetic mutations make muscle repair less well or render it susceptible to excess injury. Development of therapeutics that enhance repair, protect against injury, and reduce scar formation will benefit acutely injured muscle as well as muscle undergoing continual damage, such as in muscular dystrophy. We are currently testing novel therapeutics to enhance muscle repair and promote healing in the setting of acute muscle injury and in models of chronic muscle disease.

Development of therapeutics that enhance repair, protect against injury, and reduce scar formation will benefit acutely injured muscle as well as muscle undergoing continual damage, such as in muscular dystrophy.

How could it someday impact patient lives?

Currently, there are few treatments for muscle injury and muscle disease. Patients with muscle weakness require help with activities of daily living. Developing therapeutics to enhance membrane repair and reduce scar and stiffness in muscle are expected to improve recovery from injury, and in the case of chronic diseases like muscular dystrophy, these treatments should slow disease progression. Considering the wide range of conditions caused by cell membrane fragility and fibrotic scarring, these agents are anticipated to have clinical applications for acute injuries, post-surgical wound healing, myocardial infarction, and even sports injuries.

Considering the wide range of conditions caused by cell membrane fragility and fibrotic scarring, these agents are anticipated to have clinical applications for acute injuries, post-surgical wound healing, myocardial infarction, and even sports injuries.