title: Full functional rescue of a complete muscle (TA) in dystrophic hamsters by adeno-associated virus vector-directed gene therapy.
abstract: Limb girdle muscular dystrophy (LGMD) 2F is caused by mutations in the delta-sarcoglycan (SG) gene. Previously, we have shown successful application of a recombinant adeno-associated virus (AAV) vector for genetic and biochemical rescue in the Bio14.6 hamster, a homologous animal model for LGMD 2F (J. Li et al., Gene Ther. 6:74-82, 1999). In this report, we show efficient and long-term delta-SG expression accompanied by nearly complete recovery of physiological function deficits after a single-dose AAV vector injection into the tibialis anterior muscle of the dystrophic hamsters. AAV vector treatment led to more than 97% recovery in muscle strength for both the specific twitch force and the specific tetanic force, when compared to the age-matched control. Vector treatment also prevented pathological muscle hypertrophy and resulted in normal muscle weight and size. Finally, vector-treated muscle showed substantial improvement of the histopathology. This is the first report of successful functional rescue of an entire muscle after AAV-mediated gene delivery. This report also demonstrates the feasibility of in vivo gene therapy for LGMD patients by using AAV vectors.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. xiaox+@pitt.edu
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: Y P
authors.initials: YP
authors.lastname: Tsao
authors.forename: D
authors.initials: D
authors.lastname: Dressman
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: J F
authors.initials: JF
authors.lastname: Watchko
mesh_terms: D000818:Animals; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000008:administration & dosage / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000235:genetics*; D008647:Mesocricetus; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009136:Muscular Dystrophies / Q000628:therapy*; D049031:Sarcoglycans; D016896:Treatment Outcome
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049031:Sarcoglycans