title: Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy.
abstract: Nine patients with Duchenne or Becker muscular dystrophy were injected via the radialis muscle with a full-length human dystrophin plasmid, either once with 200 or 600 microg of DNA or twice, 2 weeks apart, with 600 microg of DNA. In the biopsies taken 3 weeks after the initial injection, the vector was detected at the injection site in all patients. Immunohistochemistry and nested reverse transcription-polymerase chain reaction indicated dystrophin expression in six of nine patients. The level of expression was low (up to 6% weak, but complete sarcolemmal dystrophin staining, and up to 26% partial sarcolemmal labeling). No side effects were observed, nor any cellular or humoral anti-dystrophin responses. These results suggest that exogenous dystrophin expression can be obtained in Duchenne/Becker patients after intramuscular transfer of plasmid, without adverse effects, hence paving the way for future developments in gene therapy of hereditary muscular diseases.
authors.affiliation: Institut de Myologie, INSERM U582, CHU Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.forename: Serge
authors.initials: S
authors.lastname: Braun
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Morris
authors.forename: Annie
authors.initials: A
authors.lastname: Barois
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Christine
authors.initials: C
authors.lastname: Payan
authors.forename: Véronique
authors.initials: V
authors.lastname: Ortega
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Boch
authors.forename: Lise
authors.initials: L
authors.lastname: Lejean
authors.forename: Christine
authors.initials: C
authors.lastname: Thioudellet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mourot
authors.forename: Christophe
authors.initials: C
authors.lastname: Escot
authors.forename: Aurore
authors.initials: A
authors.lastname: Choquel
authors.forename: Dominique
authors.initials: D
authors.lastname: Recan
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Kaplan
authors.forename: George
authors.initials: G
authors.lastname: Dickson
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Valérie
authors.initials: V
authors.lastname: Molinier-Frenckel
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Guillet
authors.forename: Patrick
authors.initials: P
authors.lastname: Squiban
authors.forename: Serge
authors.initials: S
authors.lastname: Herson
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D016189:Dystrophin / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D016189:Dystrophin; D012333:RNA, Messenger