Exon skipping therapy for Duchenne muscular dystrophy

• Published in: Advanced drug delivery reviews Vol. 87; pp. 104 - 107
• Main Authors: Kole, Ryszard, Krieg, Arthur M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29-06-2015
• Subjects: Animals; Clinical trials; Drisapersen; Dystrophin - biosynthesis; Dystrophin - genetics; Eteplirsen; Exon skipping; Exons - genetics; Humans; Morpholinos; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - genetics; Mutation; Oligonucleotides - administration & dosage; Oligonucleotides - adverse effects; Oligonucleotides - chemistry; Oligonucleotides - therapeutic use; Randomized Controlled Trials as Topic; RNA splicing; RNA Splicing - drug effects; RNA Splicing - genetics; RNA therapeutics; Clinical trials; RNA therapeutics; Drisapersen; Exon skipping; Eteplirsen; RNA splicing
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2015.05.008

Duchenne muscular dystrophy (DMD) is caused mostly by internal deletions in the gene for dystrophin, a protein essential for maintaining muscle cell membrane integrity. These deletions abrogate the reading frame and the lack of dystrophin results in progressive muscle deterioration. DMD patients experience progressive loss of ambulation, followed by a need for assisted ventilation, and eventual death in mid-twenties. By the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced. Two oligonucleotide drugs that induce desired exon skipping are currently in advanced clinical trials.
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