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 distance walked in 12 min, plasma
lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 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 any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of
phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile.