title: Current status of pharmaceutical and genetic therapeutic approaches to treat DMD.
abstract: Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article.
authors.affiliation: Department of Neurosciences, CHUL Research Center, Quebec City, Quebec, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pichavant
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
authors.forename: Paula R
authors.initials: PR
authors.lastname: Clemens
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
authors.forename: George
authors.initials: G
authors.lastname: Dickson
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Steve D
authors.initials: SD
authors.lastname: Wilton
authors.forename: Jon A
authors.initials: JA
authors.lastname: Wolff
authors.forename: Christine I
authors.initials: CI
authors.lastname: Wooddell
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D016189:Dystrophin / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015316:Genetic Therapy; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D010069:Oxadiazoles / Q000627:therapeutic use
chemical_list: D016189:Dystrophin; D005839:Gentamicins; D010069:Oxadiazoles; C515878:ataluren