Gene therapy for Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy is a severe neuromuscular disorder for which there is currently no cure. Years of research have come to fruition during the past 18 months with publications on clinical trials for several gene therapy approaches for Duchenne muscular dystrophy. This review covers the present status of these approaches. The exon skipping approach is most advanced in the process of clinical application. Encouraging results have been obtained in two systemic clinical trials and further optimization has increased delivery to the heart in animal models. Limitations of the approach are the mutation-specificity and the anticipated requirement for lifelong treatment. Gene therapy by means of gene transfer holds the promise of more long-lasting effects. Results of a first, early-stage gene therapy trial, using viral vectors to deliver a minidystrophin gene, were reported. Animal studies suggest that it may be possible to overcome the main challenges currently facing gene therapy (immunogenicity of the vector and systemic body-wide delivery). Significant steps have been made in the development of gene therapy approaches for Duchenne muscular dystrophy. These approaches aim to slow down disease progression, requiring robust outcome measures to assess efficacy.