NIH and UNR Med researchers use unsuccessful cancer therapy to treat DMD

Researchers at the National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS) and the University of Nevada, Reno School of Medicine (UNR Med) have shown that an unsuccessful cancer treatment can be a potential therapy for Duchenne muscular dystrophy (DMD).

The drug candidate SU9516 was previously developed as a treatment for leukaemia and represents a different kind of approach for treating DMD, a degenerative muscle disease caused by a faulty gene.

DMD usually begins in childhood and leads to progressive muscle weakness with no available cure, and often causes the death of the patient around the age of 25.

Patients suffering from DMD lack dystrophin, a protein similar to a molecular shock absorber that helps keep muscle cells intact. Without this, the patient’s muscles become fragile and easily injured.

Patients with DMD lose muscle strength and the ability to repair damaged muscle tissue, and mostly die from heart or respiratory issues.

The SU9516 drug, instead of fixing or replacing the faulty gene, boosts the muscle repair process that helps reinforce the muscle structure.

NCATS chemical genomics centre acting branch chief Dr Juan Marugan and UNR Med pharmacology professor Dr Dean Burkin led a team that screened more than 350,000 compounds to find SU9516.

"The study revealed that the compound enhanced muscle function in both laboratory and animal DMD models."

The study revealed that the compound enhanced muscle function in both laboratory and animal DMD models.

Burkin and his UNR Med team also collaborated with NCATS researchers to screen a large collection of compounds for molecules that could increase the levels of a cell structural protein, α7β1 integrin, in mouse muscle cells developed in the laboratory.

The research showed that SU9516 helped increase integrin production and promoted the formation of muscle cells and fibres from DMD muscle stem cells, which is another major indication of its potential as a drug.

According to Burkin, the drug can either be used alone or in combination with other therapies yet to be developed.

Image: Diaphragm muscle from SU9516 treated dystrophin-deficient mouse showing nuclei (blue), myofibres (outlined in red) and regenerating muscle fibres (green). Photo: courtesy of Burkin lab at the University of Nevada, Reno School of Medicine.