rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice.
Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, cardiac and limb musculature of these mice, considerably reducing skeletal muscle pathology and extending lifespan. These findings suggest rAAV vector-mediated systemic gene transfer may be useful for treatment of serious neuromuscular disorders such as Duchenne muscular dystrophy.
Gregorevic
Paul
P
Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
Allen
James M
JM
Minami
Elina
E
Blankinship
Michael J
MJ
Haraguchi
Miki
M
Meuse
Leonard
L
Finn
Eric
E
Adams
Marvin E
ME
Froehner
Stanley C
SC
Murry
Charles E
CE
Chamberlain
Jeffrey S
JS
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics* / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008136:Longevity; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D012132:Respiratory Muscles / Q000503:physiopathology*
D016189:Dystrophin