A new double-blind placebo-controlled clinical trial showed that the drug eteplirsen can halt the progression of Duchenne’s muscular dystrophy. The results of the study, published in the journal Annals of Neurology, show the efficacy of this drug without side effects, and could be important for future neuromuscular disease therapies.
DMD is a genetic disorder. An inherited, or sometimes a spontaneous, change (mutation) in the gene called dystrophin leads to the production of a truncated or dysfunctional dystrophin protein in the muscles. Dystrophin is an important protein for the muscle fibers as it protects them when they contract. Without dystrophin, fibers, and subsequently the muscles, slowly deteriorate. DMD starts in the very early years of life and progressively causes muscle weakness. By the age of 10-14, children can not walk and require a wheelchair; by adulthood or soon after they might succumb to cardiac and respiratory problems, as the heart and the lungs fail.
A couple of years ago, researchers have found a method to repair the abnormal dystrophin in patients’ muscles. This method is called exon skipping. It works as a molecular patch that restores the missing part of dystrophin and several drugs have been used.
Clinicians at the Nationwide Children’s hospital, led by Jerry R. Mendell, Professor of Pediatrics and Neurology, used 12 boys 7-13 years old which all had truncated dystrophin and divided them in three groups. In one group boys were injected with a middle dose of eteplirsen, the other group with a higher dose and the last group had a placebo. Before the treatment and at certain time points, the clinicians took biopsies from the boys’ arms to measure the amount of dystrophin.
After 12 weeks, they noticed an increase in functional dystrophin levels in the muscle of the boys in the eteplirsen-treated groups when compared to the amounts before the start of the treatment. But there was no change in the placebo group. After 24 weeks, the increase was even higher, significantly different from the placebo. The tests showed clearly that the drug could repair dystrophin and reverse some damage in muscles. After that realization, the researchers injected the placebo group with the drug, and 24 weeks later (the 48th week of the trial) the placebo group showed increased levels of dystrophin as well.
Most of the treated boys also showed an improvement (more than 60 meters increase) in a mobility test (60minute walk test – 6MWT) which evaluates mobility by measuring how many meters the boys can walk in 6 minutes. The walk test showed a stabilization in ambulation over time as a result of the accumulation of dystrophin.
For the duration of the treatment (48 weeks) no side effects were observed, giving hope that this can be an effective therapy should a bigger clinical trial (with more patients) confirm. But eteplirsen is a specialized molecule to treat DMD patients with a specific dystrophin mutation, called exon skipping 51, which accounts for about 13 percent of DMD patients. Dystrophin is a big protein and one molecular patch will not work for everyone. It is, nevertheless, a precursor and example of the therapies to come against the other dystrophin mutations. If approved by the F.D.A., eteplirsen could be the first therapy for DMD.