Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy

Skipping multiple exons at the same time, by using a combination of antisense oligonucleotides, offers the potential to treat a significant number of Duchenne patients. This would address one of the major limitations of current antisense therapy, in that the approach is “personalized” and designed to skip a single exon.

Specifically, exons 45 to 55 cover the main mutation “hotspot” of the DMD gene and this area is thought to harbor mutations that are present in more than half of Duchenne patients.

Individuals with this specific 45-55 deletion show almost asymptomatic skeletal muscle involvement or exceptionally mild clinical symptoms and it is this observation that has spurred interest in developing strategies for multi-exon skipping.

This review (http://www.hindawi.com/journals/bmri/2013/402369/), by leading researchers in the field of multiexon skipping, highlights novel findings from a DMD mouse model utilizing systemic multiexon skipping targeting exons 45–55.

The authors highlight the hurdles and limitations impeding the clinical translation of this approach and provide a perspective on the opportunity for exon 45–55 skipping in DMD patients.

Title: Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy.

Ref. BioMed Research International, Volume 2013 (2013), http://dx.doi.org/10.1155/2013/402369

Authors: Yoshitsugu Aoki, Toshifumi Yokota, and Matthew J. A. Wood