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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
Journal article   Peer reviewed

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

J.Mc.C. Howell, K.R. Walker, L. Davies, E. Dunton, A. Everaardt, N. Laing and G. Karpati
Neuromuscular Disorders, Vol.18(3), pp.248-258
2008
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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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.271 Lysosomal Storage Disorders
1.271.2265 Glycogen Storage Diseases
Web Of Science research areas
Clinical Neurology
Neurosciences
ESI research areas
Neuroscience & Behavior
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