June 19, 2017Neurology
Duchenne muscular dystrophy (DMD) is a degenerative muscle disease that usually begins in childhood and has no known cure. It is caused by a faulty gene that leads to progressive muscle weakness, with death often occurring around age 25. 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.
According to an article published in Molecular Therapy (June 2017), 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 DMD. The candidate drug, SU9516, represents a different kind of approach for treating DMD. Rather than trying to fix or replace the broken gene, SU9516 ramps up the muscle repair process, helping reinforce muscle structure. To accomplish this, the research team 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.
In earlier research, the senior author of the current study showed that boosting the levels of a cell structural protein, a7beta1 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. The screening exercise searched for compounds for molecules that could increase a7beta1 integrin production in mouse muscle cells grown in the laboratory. The screen revealed that SU9516 raised integrin production and promoted the formation of muscle cells and fibers from DMD muscle stem cells, another important indication of its potential as a drug. In a series of pre-clinical experiments, the authors showed that SU9516 increased the production of a7?1 integrin in human and mouse DMD muscle cells. Subsequent tests found SU9516 improved muscle function and slowed indicators of disease progression. The authors suggests that such a drug could be used alone, or in combination, with other therapies yet to be developed, and that there might also be a wide ranging applications to other muscle-damaging conditions, like cachexia, a wasting syndrome characterized by weight loss and muscle atrophy that is often seen in the late stages of cancers, and the effects of aging and injury.