Randomized placebo-controlled trial of sodium valproate in progressive supranuclear palsy

•Inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for PSP.•We assessed the safety and efficacy of sodium valproate (VPA), a GSK-3 inhibitor, in PSP.•VPA was not effective as a disease-modifying agent in PSP.

ObjectivesResults from preclinical studies suggest that inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for tauopathies. The aim of the present study was therefore to determine the effects of sodium valproate (VPA), a GSK-3 inhibitor, on disease progression in progressive supranuclear palsy (PSP).Patients and methodsWe performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500 mg/day) or matching placebo for 24 months. The primary endpoint was the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 12 and 24 months. Secondary endpoints evaluated the effects of VPA on cognitive and behavioral status (MMSE, Mattis Dementia Rating Scale, Wisconsin Card Sorting, Gröber and Buschke and Oral Denomination 80 tests), tolerability of treatment, and patient compliance.ResultsThere were no baseline differences between active treatment and placebo groups in age and clinical rating scores. PSPRS score at 12 months was significantly higher in the VPA than in the placebo group (60.8 ± 20 versus 46.9 ± 18.6 respectively, p = 0.01), but was similar between the two groups at 24 months. No significant differences were observed between VPA and placebo groups for the secondary endpoints.ConclusionOur results suggest that VPA is not effective as a disease-modifying agent in PSP.