title: Adenovirus and adeno-associated virus-mediated delivery of human myophosphorylase cDNA and LacZ cDNA to muscle in the ovine model of McArdle's disease: expression and re-expression of glycogen phosphorylase.
abstract: At present there is no satisfactory treatment for McArdle's disease, deficiency of myophosphorylase. Injection of modified adenovirus 5 (AdV5) and adeno-associated virus 2 (AAV2) vectors containing myophosphorylase expression cassettes, into semitendinosus muscle of sheep with McArdle's disease, produced expression of functional myophosphorylase and some re-expression of the non-muscle glycogen phosphorylase isoforms (both liver and brain) in regenerating fibres. Expression of both non-muscle isoforms was also seen after control injections of AdV5LacZ vectors. There was up to an order of magnitude greater expression of phosphorylase after myophosphorylase vector injection than after LacZ controls (62% of sections with over 1000 positive muscle fibres, versus 7%). The results presented here suggest that the use of viral vector-mediated phosphorylase gene transfer may be applicable to the treatment of McArdle's disease and that sustained re-expression of the brain and liver isoforms should also be investigated as a possible treatment.
authors.affiliation: Department of Veterinary Biology and Biomedical Science, Murdoch University, Perth 6150, WA, Australia. J.Howell@murdoch.edu.au
authors.forename: J McC
authors.initials: JM
authors.lastname: Howell
authors.forename: K R
authors.initials: KR
authors.lastname: Walker
authors.forename: L
authors.initials: L
authors.lastname: Davies
authors.forename: E
authors.initials: E
authors.lastname: Dunton
authors.forename: A
authors.initials: A
authors.lastname: Everaardt
authors.forename: N
authors.initials: N
authors.lastname: Laing
authors.forename: G
authors.initials: G
authors.lastname: Karpati
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001706:Biopsy; D018076:DNA, Complementary / Q000235:genetics / Q000494:pharmacology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D024982:Glycogen Phosphorylase, Muscle Form / Q000235:genetics* / Q000378:metabolism; D006012:Glycogen Storage Disease Type V / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007763:Lac Operon; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D010503:Periodic Acid-Schiff Reaction; D012756:Sheep; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D024982:Glycogen Phosphorylase, Muscle Form; D001616:beta-Galactosidase