title: rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice.
abstract: 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.
authors.affiliation: Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Gregorevic
authors.forename: James M
authors.initials: JM
authors.lastname: Allen
authors.forename: Elina
authors.initials: E
authors.lastname: Minami
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blankinship
authors.forename: Miki
authors.initials: M
authors.lastname: Haraguchi
authors.forename: Leonard
authors.initials: L
authors.lastname: Meuse
authors.forename: Eric
authors.initials: E
authors.lastname: Finn
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Adams
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
mesh_terms: 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*
chemical_list: D016189:Dystrophin