Results of an open label feasibility study of sodium valproate in people with McArdle disease

Renata S. Scalco, Mads Stemmerik, Nicoline Løkken, Christoffer R. Vissing, Karen L. Madsen, Zuzanna Michalak, Jatin Pattni, Richard Godfrey, George Samandouras, Paul Bassett, Janice L. Holton, Thomas Krag, Ronald G. Haller, C. Sewry, Ralph Wigley, John Vissing, Ros Quinlivan

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
JournalNeuromuscular Disorders
DOIs
StateAccepted/In press - 2020

Keywords

  • 12 min walking test
  • Glycogen storage disease type V
  • Outcome measures
  • Sodium valproate (VPA)
  • VO2peak

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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  • Cite this

    Scalco, R. S., Stemmerik, M., Løkken, N., Vissing, C. R., Madsen, K. L., Michalak, Z., Pattni, J., Godfrey, R., Samandouras, G., Bassett, P., Holton, J. L., Krag, T., Haller, R. G., Sewry, C., Wigley, R., Vissing, J., & Quinlivan, R. (Accepted/In press). Results of an open label feasibility study of sodium valproate in people with McArdle disease. Neuromuscular Disorders. https://doi.org/10.1016/j.nmd.2020.04.009