Muscular Dystrophy Association Grant Could Lead to Ground-Breaking Treatment

A new grant award will allow an investigator at The Children’s Hospital of Philadelphia to study the effectiveness of certain drugs called retinoid agonists in slowing or preventing muscle degeneration in individuals with muscular dystrophy. Findings from the study could lead to new, ground-breaking treatment for those individuals.

Muscular dystrophy is a group of genetic disorders that causes muscle weakness and loss. It causes progressive loss of muscle structure and muscle contractility, strength, and function. The disease is characterized by chronic inflammation, muscle cell death, the decrease and eventual exhaustion of satellite cells, and increase and infiltration of fat and fibrous tissue.

The human capacity to repair muscle is limited, however, resulting in an inexorable worsening of the disease over time. Current treatment options are limited to symptom management.

With a $405,000, three-year grant from the Muscular Dystrophy Association (MDA), Masahiro Iwamoto, PhD, DDS, a research scientist of the Translational Research Program in Pediatric Orthopaedics at Children’s Hospital and Research Associate Professor of Orthopedics at the University of Pennsylvania School of Medicine, will test his hypothesis that a retinoic acid receptor-gamma (RARg) agonist, a synthetic retinoid which selectively activates RARg could be used to slow and even stop the disease progression of muscular dystrophy.

Retinoic acid, an active form of vitamin A, plays an important role in the functioning of numerous organs, including musculoskeletal systems. However, the clinical use of natural retinoids is limited to the treatment of certain malignant tumors and skin conditions due to side effects caused by the simultaneous activation of multiple retinoid receptors. To improve drug effectiveness and reduce side effects, synthetic receptor-specific retinoid agonists have been developed.

Dr. Iwamoto and his team recently discovered that a class of selective RARg agonist block the formation of bone within muscle and prevents muscle degeneration. The findings were part of his research into heterotopic ossification (HO), the pathological formation of ectopic bone within soft tissue, primarily skeletal muscles.

More than 10 percent of patients undergoing invasive surgeries can develop a form of HO and 65 percent of seriously wounded soldiers also develop the disease, which causes chronic pain, limited motion and other complications.

With the MDA grant, Dr. Iwamoto will build on his HO research to learn more about RARg properties and how the molecule contributes to the repair and maintenance of skeletal muscle.  An RARg agonist known as R667 has already shown some promise in the lab and has been tested in humans for other conditions. Dr. Iwamoto will test whether R667 has the potential for treating muscular dystrophy in mice without serious side effects.