Emerging genetic therapies to treat Duchenne muscular dystrophy
- 1 October 2009
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Neurology
- Vol. 22 (5), 532-538
- https://doi.org/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
This publication has 50 references indexed in Scilit:
- Rational Design of Antisense Oligomers to Induce Dystrophin Exon SkippingMolecular Therapy, 2009
- Enhanced Exon-skipping Induced by U7 snRNA Carrying a Splicing Silencer Sequence: Promising Tool for DMD TherapyMolecular Therapy, 2009
- Cationic PMMA Nanoparticles Bind and Deliver Antisense Oligoribonucleotides Allowing Restoration of Dystrophin Expression in the mdx MouseMolecular Therapy, 2009
- Octa-guanidine Morpholino Restores Dystrophin Expression in Cardiac and Skeletal Muscles and Ameliorates Pathology in Dystrophic mdx MiceMolecular Therapy, 2009
- Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppressionProceedings of the National Academy of Sciences, 2009
- By‐passing the nonsense mutation in the 4CV mouse model of muscular dystrophy by induced exon skippingThe Journal of Gene Medicine, 2008
- Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomerProceedings of the National Academy of Sciences, 2008
- Characterization of a complex Duchenne muscular dystrophy-causing dystrophin gene inversion and restoration of the reading frame by induced exon skippingHuman Mutation, 2008
- Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathologyNature Medicine, 2006
- Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophyThe Journal of Gene Medicine, 2002