Scientists now know that Duchenne muscular dystrophy (DMD) is caused by mutation in a gene that makes dystrophin, a protein critical in keeping muscle fibers strong. No treatment that prevents the disease exists. However, several are being researched, and at least one—the class of drugs called corticosteroids—has shown some benefit for the symptoms of DMD.
CORTICOSTEROIDS are beneficial for DMD but have minimal to no effect in other muscular dystrophies. Some DMD patients who have received corticosteroids do not develop scoliosis, which is a sideways curving of the spine. (People with muscular dystrophy often develop scoliosis.) “This has been a big surprise,” says Jerry R. Mendell, M.D., director of the Center for Gene Therapy at Nationwide Children's Hospital in Columbus, OH. “In some cases, it seems to have stopped the disease from progressing.” What's more, he adds, the use of corticosteroids has led to a dramatic reduction in the need for spinal surgery. However, steroids have a long list of side effects, including weight gain and behavior changes, and many patients say no to the medicine.
GENE THERAPIES use viruses stripped of infectious properties to deliver a healthy gene to specific muscles. Dr. Mendell and his colleagues recently tested this approach in eight patients with limb-girdle muscular dystrophy, another form of the disease. The gene therapy was injected into one muscle in the leg, and a placebo dose was injected into a muscle in the other leg. Only the muscle injected with the gene therapy showed evidence of the healthy protein, Dr. Mendell says. But whether increased dystrophin will lead to improved function is a question that can only be addressed in further clinical trials. From studies done in mice with DMDlike disease, the increase in dystrophin did improve function, says Dr. Mendell.
Biologic agents—such as ACE-031, developed by Acceleron Pharma—are being designed to increase muscle mass and strength. ACE-031 works by decreasing myostatin, a protein that limits muscle strength and growth. The medication is now being tested in DMD patients. A safety study conducted in healthy postmenopausal women showed an increase in lean muscle mass and muscle volume.