Molecular therapies for Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder, which is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. In DMD the dystrophin gene is mutated, which results in a deficiency of the muscle dystrophin. Although expression of dystrophin is a fundamental treatment for DMD, no effective treatment for DMD is available until now. Promising molecular therapies which are mutation-specific have been developed. Antisense oligonucleotide-mediated exon skipping that convert out-of-frame mRNA into in-frame mRNA, thereby enabling semifunctional dystrophin production, is recognized as the most promising treatment for DMD. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence induced exon skipping and produced the dystrophin protein in DMD case for the first time. After extensive studies, antisense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations. The clinical effectiveness of gentamicxin and PTC124 has been reported. We have demonstrated the effectiveness of arbekacin-mediated read-through in vitro. We have already begun an investigator initiated clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.