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Pre-MRNA splicing as a therapy for duchenne muscular dystrophy

Wilton, S.D. (2018) Pre-MRNA splicing as a therapy for duchenne muscular dystrophy. Journal of Gene Medicine, 20 (1).

Link to Published Version: https://doi.org/10.1002/jgm.3003
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Abstract

Duchenne muscular dystrophy (DMD), the most common and severe form of childhood muscle wasting, is most frequently caused by frame‐shifting deletions of one or more exons that preclude functional dystrophin expression. Antisense oligonucleotides can redirect pre‐mRNA processing so that specific exons are excised from the defective dystrophin mRNA to restore the reading frame and allow expression of a functional dystrophin. Exondys 51, a phosphorodiamidate morpholino oligomer designed to excise exon 51 from the dystrophin mRNA, is relevant to the most common type of DMD‐causing mutation. This compound was granted accelerated approval by the US Food and Drug Administration in September, 2016. Exondys 51 is the first dystrophin restoring drug, as well as the first specific exon‐skipping drug, to be approved for clinical use. Additional phase 3 clinical trials have been initiated evaluating skipping of other dystrophin exons (45 or 53) in order to address different DMD mutations. Designing clinical trials to evaluate drugs for rare diseases, especially where patient numbers are small and disease progression is slow, poses great challenges. The accelerated approval of Exondys 51 has resulted in vigorous and heated discussion within and outside the FDA, and these issues will be discussed and concerns addressed. Since the majority of human genes undergo some form of splicing during expression, potential applications for therapeutic intervention during splicing could be relevant to many inherited and acquired conditions. “Therapeutic alternative splicing”is now being developed to a range of conditions, adult onset Pompe's disease to multiple sclerosis, spinal muscular atrophy to cystic fibrosis.

Publication Type: Journal Article
Murdoch Affiliation: Centre for Comparative Genomics
Publisher: John Wiley & Sons
Copyright: © 2018 John Wiley & Sons, Ltd.
Other Information: Abstract taken from the Joint 10th Australasian Gene and Cell Therapy Society (AGCTS) and Australasian Society for Stem Cell Research (ASSCR) Annual Scientific Meeting
URI: http://researchrepository.murdoch.edu.au/id/eprint/40558
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