Landmark 288 · Trial in people
LY3962681 (Lilly siRNA)
A safety test. People with Parkinson's must first have a positive spinal-fluid test for the protein.
In short
An siRNA injected into the spinal fluid is being tested for safety and for lowering spinal-fluid alpha-synuclein in up to 124 people, with Parkinson's patients required to have a positive seed-amplification test.
- What it is
- Trial in people
- Outcome
- Result due Jul 2030
- When
- 2024–2030
- Size
- 124 people · Phase 1
- Approach
- Clear the bad protein
- Research lane
- Synuclein lowering
- Trial registry
- NCT06565195
- 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
Prevail Therapeutics, a subsidiary of Eli Lilly (registered sponsor). Sites are reported in Texas and Tokyo.
What happened
- Design (NCT06565195). Phase 1, randomised, double-blind, with an artificial-spinal-fluid placebo. Started 27 August 2024; recruiting. Registry enrolment 124 (estimated); Alzforum describes 48 healthy volunteers in six single-dose cohorts and 60 patients in five cohorts, each getting two doses 12 to 24 weeks apart.
- Who is in. In the multiple-dose part, people with Parkinson's (Hoehn and Yahr stage 1 to 2.5) and a positive spinal-fluid alpha-synuclein seed amplification test (landmark 9).
- Aims. Primary: serious and other adverse events. Secondary: drug levels and change in spinal-fluid total alpha-synuclein. Estimated completion 23 July 2030 (Alzforum gave May 2029 in mid-2025).
- Preclinical. The 2024 MDS abstract reports dose-dependent, lasting falls in SNCA RNA and protein in primate brain, including the substantia nigra and striatum, and a clean toxicology study. It gives no percentages.
Why it moved us toward a cure
It tests the lowering idea from landmark 14 with a drug designed to act for months per dose. Spinal-fluid delivery of a gene-silencing drug was proven in people by nusinersen (landmark 256). Mice without synuclein stay healthy (landmark 201). Siblings: landmark 287 and landmark 289.
Outcome
Pending. No results. Limited to safety and target engagement.
Sources
- ClinicalTrials.gov NCT06565195 (API read 19 Oct 2026; updated 16 Oct 2026)
- Alzforum LY3962681
- MDS 2024 abstract
- Not yet verified: the split between healthy and patient numbers (Alzforum only); any interim data.
How it connects
Built on
- builds on Synuclein knockout mice are viable · 2000
- tests Extra copies of the synuclein gene cause Parkinson's · 2003
- uses Nusinersen: intrathecal antisense works · 2016
- uses Seed amplification assay · 2023
Led to
None recorded.