Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy

The use of antisense oligonucleotides (AON) to induce exon skipping in precursor mRNA is at the forefront of clinical research for the treatment of DMD. The most advanced programs from Sarepta Therapeutics and GSK/Prosensa target exon 51, and are currently in Phase II and Phase III clinical trails in the US and the rest of the world. Their approval is anticipated within the near future.

Strategies that could enhance or improve the efficiency of the current (and future) exon skipping drugs to produce novel dystrophin have been sought by a number of research groups over the last few years. Now a recent report by Kendall et al. describes the identification of a compound that enhances the efficiency of exon skipping in vitro and in vivo. The compound, the approved drug Dantrolene, works in concert with the exon skipping drug to restore dystrophin levels in the mdxmice and also in reprogrammed myotubes from DMD patients. This research offers insight into the exon skipping process, and could provide a fast track opportunity to use an approved drug to enhance the efficiency of current exon skipping drugs in future clinical trials.