Emerging genetic therapies to treat Duchenne muscular dystrophy.
OBJECTIVE
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'.


RESULTS
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.


CONCLUSIONS
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.
Nelson
Stanley F
SF
Department of Physiological Science, UCLA, Los Angeles, CA 90095-7334, USA.
Crosbie
Rachelle H
RH
Miceli
M Carrie
MC
Spencer
Melissa J
MJ
D018388:Codon, Terminator; D016189:Dystrophin / Q000235:genetics; D005091:Exons; D006801:Humans; D060172:Morpholinos; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D009841:Oligonucleotides / Q000627:therapeutic use*; D010069:Oxadiazoles / Q000627:therapeutic use*
D018388:Codon, Terminator; D016189:Dystrophin; D060172:Morpholinos; D009841:Oligonucleotides; D010069:Oxadiazoles; C525434:PRO051; C000611335:eteplirsen; C515878:ataluren