title: Eteplirsen in the treatment of Duchenne muscular dystrophy.
abstract: Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500-5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in theDMDgene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame ofDMDthrough specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients withDMDmutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta.
authors.forename: Kenji Rowel Q
authors.initials: KR
authors.lastname: Lim
authors.affiliation: Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta.
authors.forename: Rika
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta; The Friends of Garrett Cumming Research & Muscular Dystrophy Canada, HM Toupin Neurological Science Research Chair, Edmonton, AB, Canada.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000818:Animals; D006801:Humans; D060172:Morpholinos / Q000627:therapeutic use*; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*
chemical_list: D060172:Morpholinos; C000611335:eteplirsen
keywords: Duchenne muscular dystrophy; Exondys 51; eteplirsen; exon-skipping therapy; phosphorodiamidate morpholino oligomers