Results of an open label feasibility study of Sodium Valproate in people with McArdle disease

ABSTRACT McArdle disease results from a lack of Muscle Glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total walked distance in 12 minutes, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters were collected. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in either the primary outcome VO2peak between baseline and 6 months of treatment or any other secondary outcomes. Treatment with VPA does not benefit people with McArdle disease.