Researchers aim to repurpose former experimental cancer therapy to treat muscular dystrophy

WASHINGTON, June 13, 2017 /PRNewswire-USNewswire/ -- Researchers at the National Institutes of Health's National Center for Advancing Translational Sciences (NCATS) and the University of Nevada, Reno School of Medicine (UNR Med) have demonstrated that a drug originally targeted unsuccessfully to treat cancer may have new life as a potential treatment for Duchenne Muscular Dystrophy (DMD).

The candidate drug, SU9516, represents a different kind of approach for treating DMD, a degenerative muscle disease that usually begins in childhood and has no cure. It is caused by a faulty gene that leads to progressive muscle weakness, with death often occurring around age 25. Rather than trying to fix or replace the broken gene, SU9516 instead ramps up the muscle repair process, helping reinforce muscle structure.

NCATS Chemical Genomics Center Acting Branch Chief Juan Marugan, Ph.D., and UNR Med Professor of Pharmacology Dean Burkin, Ph.D., led a team that screened more than 350,000 compounds to find SU9516, which had been previously developed as a treatment for leukemia. The research demonstrated that this compound improved muscle function in both laboratory and animal DMD models. The results, published recently in Molecular Therapy, may provide a promising approach against the disorder and other muscle-wasting conditions.

Those with DMD lack dystrophin, a protein akin to a molecular shock-absorber that helps keep muscle cells intact. Without dystrophin, muscles are fragile and easily injured. Individuals lose muscle strength and the ability to repair damaged muscle tissue. Most die from heart or respiratory problems.

In earlier research, Burkin and his colleagues showed that boosting the levels of a cell structural protein, α7β1 integrin, in affected muscle cells could alleviate DMD symptoms in a mouse model. In addition, increased amounts of the protein slowed the disease's progress.

Pre-clinical experiments also showed that SU9516 increased the production of α7β1 integrin in human and mouse DMD muscle cells. Subsequent tests found SU9516 improved muscle function and slowed indicators of disease progression.

"Our findings open the door to develop new drug treatments for DMD," Marugan said.

The NCATS-UNR team plans to work with medicinal chemists to make the molecule more specific for DMD, with a goal of future testing in patients.  

The work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Cure CMD and Struggle Against Muscular Dystrophy.

For more information, visit https://ncats.nih.gov.

Media Contact: Geoff Spencer, [email protected]; Jane Tors, 775-327-2359 office, [email protected]

SOURCE University of Nevada, Reno School of Medicine; National Institutes of Health’s National Center for Advancing Translational Sciences