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McArdle’s disease is an inherited myopathy caused by the absence of the muscle isoform of phosphorylase. There is no treatment. In normal muscle the genes for the brain and liver isoforms are active in utero, in neonates and in regenerating mature muscle. This activity was found in mature muscle in McArdle’s disease sheep following the injection of vectors carrying cDNA for LAC Z or myophosphorylase or the injection of notexin or valproate and resulted in a reduction of glycogen. This active phosphorylase was seen in muscle at injection sites. Successful treatment of McArdle’s disease must involve all muscles and would have to be systemic rather than local. Therefore valproate was administered via the alimentary tract. Initially valproate syrup was given to 7 affected sheep. A muscle biopsy taken from each sheep before treatment did not contain phosphorylase positive fibres. Samples were taken from 7 muscles from each sheep at the end of the trial and 2,240 phosphorylase positive fibres were seen in muscle from 5 of the 7 sheep in fibres of normal appearance. Levels of valproate in blood within the pharmacologically active range were recorded throughout treatment. A new trial has commenced using enteric coated valproate tablets in an attempt to induce blood levels of valproate in the pharmacologically active zone for a longer period of time. Exercise tolerance is also being recorded in this trial. A biopsy was taken after 3 weeks of dosing and 1322 positive fibres were found in 4 of the sheep. The trial is continuing.
McArdle’s Treatment Trial