Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. In conjunction with exon skipping AON therapy, this review highlights progress in viral gene therapy-which although laced with a chequered past, has come of age. Notwithstanding challenges, such as combating the delivery of a large sized RNA and the difficulty of targeting all muscles, considerable advancement is observed in optimising viral therapy. The authors also discuss the drug Ataluren which has “demonstrated proof of principle of reading through stop codons as an approach to therapy” but has yet to show clinical safety and efficacy. A promising treatment strategy highlighted in this article is increasing the levels of Utrophin, which is a dystrophin related protein that can functionally compensate for dystrophin in mdx mouse. Although clinical trials are underway for this type of treatment, whether utrophin levels in patients can be increased to the levels where therapeutic benefit will be observed is unknown. There is much accomplished in this field and many challenges to overcome to arrive at the optimal treatment of DMD, but the authors believe that the substantial improvement from the past 5 years is a good indication of things to come.
