Category: Parkinson’s Disease: Clinical Trials
Objective: To evaluate the continued safety, pharmacokinetics (PK), and pharmacodynamics of VQ-101 in patients with Parkinson’s disease (PD) with and without a GBA1 mutation.
Background: Heterozygous mutations in the GBA1 gene result in a 20-50% reduction in glucocerebrosidase (GCase) activity and are a major risk factor for the development of PD. VQ-101 is a fully CNS-penetrant allosteric activator of lysosomal GCase that is in clinical development for the treatment of GBA-PD. In preclinical studies using iPSC-derived dopaminergic neurons from GBA-PD patients, >50% activation of GCase by VQ-101 was shown to significantly block the accumulation of misfolded alpha synuclein. In initial clinical studies, a dose-dependent increase in GCase activity by VQ-101 was successfully demonstrated in healthy volunteers and in PD patients with and without a GBA1 mutation for up to 3 months.
Method: 200 mg/day of VQ-101 was evaluated in a 28-day, double blind, placebo-controlled trial, followed by 6 months of open label in patients with PD. GCase activation was assessed using an analytically validated lysosomal assay. Clinical outcome assessments, plasma and CSF samples were collected for exploratory analyses, including target and pathway engagement biomarkers.
Results: 40 subjects, 20 with and 20 without a GBA1 mutation were enrolled in the study. VQ-101 showed a favorable safety profile with no discontinuations due to adverse events (AEs) and with 97% of AEs reported as mild or transient, with most associated with study procedures. VQ-101 showed full CNS penetrance and a PK profile supporting once daily dosing. Lysosomal GCase activity increased >75% and was maintained for the duration of the study.
Conclusion: In people with PD with and without a GBA1 mutation, once daily VQ-101 continues to demonstrate favorable tolerability, full CNS penetrance, and sustained target and pathway engagement supporting the potential for VQ-101 to slow or stop the progression of Parkinson’s disease.
To cite this abstract in AMA style:
M. Facheris, J. Valk, I. Koopmans, K. Hunt, M. Hagey, O. Siddiqui, P. Kremer, J. Sullivan, D. Ysselstein. The Allosteric Activator of Lysosomal Glucocerebrosidase VQ-101 Demonstrates Robust Evidence of Target and Pathway Engagement in People with Parkinson’s Disease: Results from a 6-Month Open-Label Extension Study [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/the-allosteric-activator-of-lysosomal-glucocerebrosidase-vq-101-demonstrates-robust-evidence-of-target-and-pathway-engagement-in-people-with-parkinsons-disease-results-from-a-6-month-open-label-ext/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-allosteric-activator-of-lysosomal-glucocerebrosidase-vq-101-demonstrates-robust-evidence-of-target-and-pathway-engagement-in-people-with-parkinsons-disease-results-from-a-6-month-open-label-ext/