Gene therapy for Duchenne muscular dystrophy

Abstract

Gene therapy has great potential to treat Duchenne muscular dystrophy. Among many proposed strategies to deliver a therapeutic gene to muscle, recombinant adeno-associated virus-mediated gene transfer is the most promising. The recent isolation of new adeno-associated virus serotypes from human and nonhuman primates provides the opportunity to develop vectors that can achieve the long-term expression of a therapeutic gene in muscles of the entire body without detrimental effects. To translate the results from small animal models to clinical trials in humans, further work using larger animal models, such as dystrophic dogs or nonhuman primates, is required. This review also discusses recent progress in other gene transfer-related therapeutic approaches, including targeted exon skipping and gene correction.

Keywords: :

• adeno-associated virus vector
• Duchenne muscular dystrophy
• dystrophin
• exon skipping
• gene therapy

Acknowledgements

The authors are grateful to A Nishiyama and T Yokota for discussion and E Takahashi for help in preparing this manuscript. Studies in the authors‘ laboratory are supported by a Grant for Research on Nervous and Mental Disorders (16B-2), and Health Science Research Grants for Research on the Human Genome and Gene Therapy (H16-genome-003), for Research on Brain Science (H15-Brain-021, H18-Brain-019) from the Ministry of Health, Labor and Welfare, and Grants-in-Aid for Scientific Research (16590333, 18590392) from the Ministry of Education, Culture, Sports, Science and Technology.