Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy.
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.
Romero
Norma B
NB
Institut de Myologie, INSERM U582, CHU Pitié-Salpêtrière, 75013 Paris, France.
Braun
Serge
S
Benveniste
Olivier
O
Leturcq
France
F
Hogrel
Jean-Yves
JY
Morris
Glenn E
GE
Barois
Annie
A
Eymard
Bruno
B
Payan
Christine
C
Ortega
Véronique
V
Boch
Anne-Laure
AL
Lejean
Lise
L
Thioudellet
Christine
C
Mourot
Brigitte
B
Escot
Christophe
C
Choquel
Aurore
A
Recan
Dominique
D
Kaplan
Jean-Claude
JC
Dickson
George
G
Klatzmann
David
D
Molinier-Frenckel
Valérie
V
Guillet
Jean-Gérard
JG
Squiban
Patrick
P
Herson
Serge
S
Fardeau
Michel
M
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
D016189:Dystrophin; D012333:RNA, Messenger