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What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy?

Wells, D J


D J Wells


Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle wasting disease. The disease is due to mutations in the DMD gene that encodes for a large intracellular protein called dystrophin. Dystrophin plays a critical role in linking the internal cytoskeleton of the striated muscle cell with the extracellular matrix as well as having cell signalling functions. In its absence muscle contraction is associated with cycles of damage, repair, inflammation and fibrosis with eventual loss of muscle and replacement with fat. Experiments in animal models of DMD have generated a number of different approaches to the induction of dystrophin including viral vector mediated delivery of a recombinant dystrophin gene, antisense oligonucleotide mediated exon-skipping to restore the open reading frame in the dystrophin mRNA, read-through of premature stop mutations, genome modification using CRISPR-Cas9 or cell based transfer of a functional dystrophin gene. In all cases, it will be important to understand how much dystrophin expression is required for a clinically effective therapy and this review examines the data from humans and animal models to estimate the percentage of endogenous dystrophin that is likely to have significant clinical benefit. While there are a number of important caveats to consider, including the appropriate outcome measures, this review suggests that approximately 20% of endogenous levels uniformly distributed within the skeletal muscles and the heart may be sufficient to largely prevent disease progression.


Wells, D. J. (2019). What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy?. Journal of Muscle Research and Cell Motility, 40(2), 141-150.

Journal Article Type Article
Acceptance Date Jun 27, 2019
Publication Date Jul 9, 2019
Deposit Date Jul 18, 2019
Publicly Available Date Jul 7, 2020
Print ISSN 0142-4319
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 40
Issue 2
Pages 141-150
Public URL


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