title: Exon skipping therapy for Duchenne muscular dystrophy.
abstract: 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.
authors.affiliation: Sarepta Therapeutics Inc., Cambridge, MA, USA. Electronic address: rkole@sarepta.com.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kole
authors.affiliation: Checkmate Pharmaceuticals, Cambridge, MA, USA.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D006801:Humans; D060172:Morpholinos; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D012326:RNA Splicing / Q000187:drug effects / Q000235:genetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D016189:Dystrophin; D060172:Morpholinos; D009841:Oligonucleotides; C525434:PRO051; C000611335:eteplirsen
keywords: Clinical trials; Drisapersen; Eteplirsen; Exon skipping; RNA splicing; RNA therapeutics