Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting p...

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Bibliographic Details
Published in:BioMed research international 2013-01, Vol.2013 (2013), p.1-8
Main Authors: Aoki, Yoshitsugu, Wood, Matthew J. A., Yokota, Toshifumi
Format: Article
Language:English
Subjects:
Age
Animals
Antisense drugs
Care and treatment
Drug Discovery
Drug Evaluation, Preclinical
Duchenne muscular dystrophy
Dystrophin - chemistry
Dystrophin - genetics
Exons - genetics
Genetic aspects
Health aspects
Humans
Medical research
Muscular dystrophy
Muscular Dystrophy, Duchenne - drug therapy
Muscular Dystrophy, Duchenne - genetics
Muscular system
Mutation
Oligonucleotides, Antisense - genetics
Oligonucleotides, Antisense - therapeutic use
Review
Risk factors
Rodents
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Summary:Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting prospect of an effective oligonucleotide therapy has emerged which restores dystrophin protein expression to affected tissues in DMD patients with highly promising data from a series of clinical trials. This therapeutic approach is highly mutation specific and thus is personalised. Therefore DMD has emerged as a model genetic disorder for understanding and overcoming of the challenges of developing personalised genetic medicines. One of the greatest weaknesses of the current oligonucleotide approach is that it is a mutation-specific therapy. To address this limitation, we have recently demonstrated that exons 45–55 skipping therapy has the potential to treat clusters of mutations that cause DMD, which could significantly reduce the number of compounds that would need to be developed in order to successfully treat all DMD patients. Here we discuss and review the latest preclinical work in this area as well as a variety of accompanying issues, including efficacy and potential toxicity of antisense oligonucleotides, prior to human clinical trials.
ISSN:2314-6133
2314-6141
DOI:10.1155/2013/402369