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Citation
Tags
HERO ID
505051
Reference Type
Journal Article
Title
Emerging genetic therapies to treat Duchenne muscular dystrophy
Author(s)
Nelson, SF; Crosbie, RH; Miceli, MC; Spencer, MJ
Year
2009
Is Peer Reviewed?
Yes
Journal
Current Opinion in Neurology
ISSN:
1350-7540
EISSN:
1080-8248
Volume
22
Issue
5
Page Numbers
532-538
Language
English
DOI
10.1097/WCO.0b013e32832fd487
Abstract
Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called 'exon skipping' and 'nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy.
Keywords
antisense therapeutics; disease; dystrophin; dystrophy; exon skipping; mouse; muscle; nonsense codon suppression; mdx mice; skeletal-muscle; reading-frame; full-length; nonsense; mutations; systemic delivery; cystic-fibrosis; mouse model; exon; expression
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