Scalco, RS;
Stemmerik, M;
Løkken, N;
Vissing, CR;
Madsen, KL;
Michalak, Z;
Pattni, J;
... Quinlivan, R; + view all
(2020)
Results of an open label feasibility study of sodium valproate in people with McArdle disease.
Neuromuscular Disorders
, 30
(9)
pp. 734-741.
10.1016/j.nmd.2020.04.009.
Preview |
Text
NMD-D-20-00030_R1.pdf - Accepted Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Results of an open label feasibility study of sodium valproate in people with McArdle disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nmd.2020.04.009 |
| Publisher version: | https://doi.org/10.1016/j.nmd.2020.04.009 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | 12 min walking test, Glycogen storage disease type V, Outcome measures, Sodium valproate (VPA), VO2peak |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10108806 |
Archive Staff Only
 |
View Item |
