Venglustat for Patients with GBA1-Associated Parkinson Disease?

This glucosylceramide synthase inhibitor was disappointing in a phase 2 study, but similar pharmacologic approaches might eventually yield more effective results.

Mutations in the GBA1 gene are one of the most common risk factors for genetic Parkinson disease (PD). Because accumulation of glucosylceramide has been suggested as a pathogenic mechanism, these researchers conducted a manufacturer-sponsored, multi-country, double-blind, phase 2 study of oral venglustat, a brain-penetrant glucosylceramide synthase inhibitor.

The 221 study participants, who were required to have early PD (Hoehn and Yahr stage ≤2) and one or more GBA1 variants, were randomized to oral venglustat (15 mg/day) or a placebo for 1 year. Glucosylceramide concentrations in plasma and cerebrospinal fluid decreased by 75% with venglustat. No difference between groups was found at 1 year on the primary outcome measure, the Movement Dis…

Reviewing Author

Michael S. Okun, MD

Disclosures

Consultant/Advisory BoardParkinson’s Foundation; Tourette Association of America

Speaker’s BureauMedscape/WebMD CME, Movement Disorders Society CME, American Academy of Neurology CME

RoyaltiesBooks4Patients; Demos; Cambridge; Taylor and Francis; Robert Rose; Public Affairs

Grant/Research SupportNational Institutes of Health; Parkinson’s Foundation; Tourette Association of America; University of Florida Foundation

Editorial BoardsTremor and Other Hyperkinetic Movements; JAMA Neurology

Leadership Positions in Professional SocietiesParkinson’s Foundation (Medical Advisor)