Phase II Exon-Skipping Trial in Duchenne Dystrophy Raises More Questions Than It Answers

Duchenne muscular dystrophy (DMD) results from a heterogeneous group of mutations in the dystrophin gene that disrupt the transcriptional reading frame and lead to dystrophin protein deficiency. Antisense oligonucleotides (ASOs) may be used to induce “exon skipping,” thereby restoring the open reading frame and resulting in a truncated but functional dystrophin protein intended to yield a milder phenotype. Researchers conducted a phase II, randomized, placebo-controlled, manufacturer-sponsored study of drisapersen, which targets skipping of exon 51, a therapeutic strategy relevant to about 13% of DMD patients. Fifty-three patients were randomized to 48 weeks of placebo, drisapersen 6 mg/kg administered subcutaneously either continuously (on…