title: Investigating sodium valproate as a treatment for McArdle disease in sheep.
abstract: McArdle disease is due to an absence of the enzyme muscle glycogen phosphorylase and results in significant physical impairment in humans. We hypothesised that sodium valproate, an HDAC inhibitor, might have the ability to up-regulate the enzyme. We treated McArdle sheep with sodium valproate given enterically at 20-60 mg/kg body wt. Compared with untreated control animals, there was increased expression of phosphorylase in muscle fibres. The response was dose dependent and reached a maximum 2 hours after the application and increased with repeated applications. Improvement in mobility could not be demonstrated. These findings suggest that sodium valproate is a potential therapeutic treatment for McArdle disease.
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia; Australian Neuro-Muscular Research Institute, CNND, University of Western Australia, Perth, Western Australia, Australia. Electronic address: J.Howell@murdoch.edu.au.
authors.forename: J McC
authors.initials: JM
authors.lastname: Howell
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Dunton
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia.
authors.forename: K E
authors.initials: KE
authors.lastname: Creed
authors.affiliation: Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Quinlivan
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic hospital, Oswestry, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Sewry
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006012:Glycogen Storage Disease Type V / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D019344:Lactic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D006005:Phosphorylases / Q000378:metabolism; D012756:Sheep; D013997:Time Factors; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D019344:Lactic Acid; D014635:Valproic Acid; D006005:Phosphorylases; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D002118:Calcium
keywords: Glycogen phosphorylase; Glycogen storage disease type V; HDCAI; McArdle disease; Sheep; Sodium valproate