DMD: Exon-Skipping Drug Drisapersen Appears to Increase Dystrophin Levels

Multinational pharmaceutical company GlaxoSmithKline (GSK) has released encouraging results about dystrophin protein production in a phase 2, non-U.S. trial of its exon-skipping compound drisapersen in boys with Duchenne muscular dystrophy (DMD).

Dystrophin is the muscle protein missing in DMD; its absence can be caused by any of a number of mutations in the dystrophin gene. Drisapersen (also known as GSK2402968) targets exon 51 of the dystrophin gene and is being developed to treat DMD caused by mutations near this exon. It's one of two exon-skipping drugs for DMD now in clinical trials.

The findings, released in August 2013, supplement trial results released in April that showed participants who received drisapersen every week for 24 weeks ("continuous" treatment group) walked significantly farther in six minutes than those who received a placebo.

The new findings show that, at week 25 of the study, those who received drisapersen had higher dystrophin levels in a muscle sample than those who received a placebo. Specifically:

  • Thirteen of the 18 participants (72 percent) who had received dystrophin injections every week — the "continuous" group — showed more dystrophin protein in a muscle sample than they had at the start of the study (baseline).
  • Ten of the 17 participants (59 percent) who received injections of dystrophin on a different schedule — the "intermittent" group — showed more dystrophin protein than they had at baseline.
  • One child out of 18 (6 percent) in the placebo group showed more dystrophin in his muscles at week 25 than he had at baseline.

Complete results on dystrophin levels in this trial are expected in October 2013, the company has said.

A summary of results available so far for this phase 2, non-U.S. drisapersen study (called DMD114117 by GSK) can be downloaded at Results Summary for 114117.

MDA has been supporting the development of exon skipping as a strategy for the treatment of DMD since the 1990s; for more on the development of this strategy, see DMD: Exon Skipping Timeline.





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