Landmark 110 · Trial in people
LRRK2 antisense BIIB094
It lowered LRRK2 protein in an 82-person safety trial. Biogen stopped it for business reasons, not because it failed. It was never tested for benefit.
In short
A spinal-fluid antisense drug cut LRRK2 protein by up to 59% in an 82-person safety trial, but Biogen halted its development in early 2025 and it was never tested for benefit.
- What it is
- Trial in people
- Outcome
- Did not work
- When
- 2026
- Size
- 82 people · Phase 1
- Approach
- Treat the inherited causes
- Research lane
- LRRK2
- Trial registry
- NCT03976349
- 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
Omar Mabrouk and colleagues, developing the drug for Biogen and Ionis Pharmaceuticals (Biogen funded the study). Published in Nature Medicine in 2026.
What happened
LRRK2 is an enzyme that is overactive in some inherited Parkinson's and perhaps in other forms (landmark 7, 37). Instead of blocking the enzyme with a pill, as BIIB122 does, BIIB094 (ION859) is an antisense oligonucleotide: a short strand of genetic material that sends LRRK2's messenger RNA for destruction, so less protein is made. It is injected into the spinal fluid. The Phase 1 trial, REASON (NCT03976349; started Aug 2019, completed Aug 2024), had two parts. Part A: 40 people took a single dose of 10-150 mg or placebo. Part B: 42 people, stratified by LRRK2 variant status, took four doses of 40-120 mg or placebo, 4 weeks apart. Adverse events were mostly mild to moderate and none limited the dose; no serious adverse events were related to the drug. Spinal-fluid LRRK2 fell by up to 59% and its phosphorylated product pRab10 by up to 50%, whether or not people carried a mutation. Some lysosomal (the cell's recycling compartment) proteins also fell. It was not designed to show clinical benefit.
Why it moved us toward a cure
It gave the first human proof that lowering the amount of LRRK2 protein, not just its activity, is safe and measurable, and uses the same antisense approach as the synuclein-lowering drugs in landmark 29.
The intrathecal antisense route was proven in people by nusinersen (landmark 256).
Healthy people carrying one working LRRK2 copy supported the safety of lowering LRRK2 (landmark 227).
Outcome
Dead end for this molecule. Biogen's fourth-quarter 2024 results release (12 Feb 2025) listed BIIB094 in early Parkinson's among four programs it was discontinuing "as part of ongoing pipeline prioritization efforts"; no safety or efficacy reason was given. Its small-molecule relative BIIB122 later failed to slow early Parkinson's (LUMA, 2026).
Sources
- Mabrouk et al., Nature Medicine 2026;32(4):1421–1431, DOI 10.1038/s41591-026-04262-4 · news summary
- Biogen Q4 2024 results release, 12 Feb 2025 (SEC exhibit 99.1) · Fierce Biotech coverage (page blocked here) · Trial record NCT03976349 · Europe PMC, PMID 41876647
- Not yet verified: the full author list; the registry lists 62 actual participants against 82 in the paper (cause not found).
How it connects
Built on
- tests The LRRK2 gene: the first gene-based drug target · 2004
- uses Nusinersen: intrathecal antisense works · 2016
- builds on People with one broken LRRK2 copy are healthy · 2020
Led to
None recorded.