Toward an oligonucleotide therapy for Duchenne muscular dystrophy: a complex development challenge.

Antisense oligonucleotide (AO)-mediated exon skipping is a promising new therapy for Duchenne muscular dystrophy (DMD), recently demonstrating proof of principle for restoring the absent dystrophin protein in DMD patients. However, the range of AO chemistries available for exon skipping is limited; effective systemic dystrophin protein restoration has yet to be demonstrated and will be required for disease modification in patients; and the current approach is mutation-specific, necessitating the development of multiple AO drugs to treat all DMD patients. This is therefore a highly complex drug development challenge.