Landmark 69 · Trial in people
Venglustat (MOVES-PD) in GBA1 carriers
No slowing in 221 gene carriers over a year. Scores were slightly worse than on placebo.
In short
Venglustat, a pill that blocks the enzyme making GCase's raw material, did not slow early Parkinson's in 221 people with a GBA1 variant; the score trended slightly worse than on placebo.
- What it is
- Trial in people
- Outcome
- Did not work
- When
- 2023
- Size
- 221 people · Phase 2
- Approach
- Help cells clean up
- Research lane
- Lysosome & GBA
- Trial registry
- NCT02906020
- Last checked
- 19 Oct 2026
The research record
This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".
Who
Nir Giladi, Roy Alcalay and colleagues; funded by Sanofi (Lancet Neurology, 2023).
What happened
Mutations in the GBA1 gene, the commonest genetic risk factor (landmark 16), lower the activity of the enzyme GCase, which feeds a loop with alpha-synuclein (landmark 35).
Venglustat (MOVES-PD part 2) blocks glucosylceramide synthase, the enzyme that makes GCase's raw material. In this Phase 2 trial (NCT02906020), 221 people with early Parkinson's (Hoehn and Yahr stage 2 or less) and a GBA1 variant, at 52 centres in 16 countries, were randomised between December 2016 and May 2021 to 15 mg a day (110) or placebo (111) for 52 weeks. The main measure was the change in MDS-UPDRS parts II+III (96 and 105 people analysed). The MDS-UPDRS parts II+III score rose 7.29 points on venglustat versus 4.71 on placebo (difference 2.58, 95% CI -1.10 to 6.27; p = 0.17), a trend in the unfavourable direction. Serious adverse events were equal (12 people, 11%, in each group). The authors suggested this approach may not be viable.
Why it moved us toward a cure
It tested the "less raw material" end of the lysosomal pathway in people chosen by genotype. The result suggests the pathway may be too downstream, the dose or timing wrong, or the trial too short, not that genetic selection was a mistake. The opposite approach, a pill that raises GCase activity (BIA 28-6156), also failed three years later (landmark 235). Ambroxol (landmark 40) is still in Phase 3.
Outcome
Dead end for venglustat.
Sources
- Giladi et al., Lancet Neurol 2023;22(8):661–671, DOI 10.1016/S1474-4422(23)00205-3 · abstract record
- ClinicalTrials.gov NCT02906020 (the registry's count of 273 differs from the paper's 221 randomised; probably includes part 1)
- Not yet verified: MOVES-PD part 1 (Phase 1) details; why the registry count differs from the paper's.
How it connects
Built on
- builds on GBA mutations: commonest genetic risk factor · 2009
- tests GCase and synuclein feed each other · 2011
Led to
None recorded.