Task: gap023 | Last Updated: 2026-03-24 | Kind: gap-analysis | Total Gaps Identified: 6
This page addresses the critical research gap of whether LRRK2 kinase inhibition can achieve true disease modification in Parkinson's disease.
Can LRRK2 inhibition demonstrate disease modification (not only target engagement)?
This is a critical knowledge gap in Parkinson's disease (PD) therapeutics. While LRRK2 inhibitors have shown target engagement in clinical trials (BIIB122/DNL151), it remains unproven whether they can slow or halt disease progression - i.e., achieve true disease modification[1][2].
Does inhibition of LRRK2 kinase activity translate to clinical benefit?
What biomarkers can predict disease modification?
Which PD patients will benefit most from LRRK2 inhibition?
Should LRRK2 inhibitors be combined with other approaches?
| Element | Current Status | Gap |
|---|---|---|
| Clear mechanism | Established | None |
| Target engagement | Demonstrated | None |
| Clinical outcomes | Not shown | Critical |
| Biomarker correlation | Not established | Critical |
| Long-term follow-up | 2 years max | Major |
Taylor et al. LRRK2 and Parkinson's disease: from pathogenesis to treatment. Nat Rev Neurol. 2019. ↩︎
Jennings et al. LRRK2: a common pathway for Parkinson's disease and cancer?. NPJ Parkinsons Dis. 2022. ↩︎
BIIB122 Study Group. LRRK2 kinase inhibition with BIIB122 in Parkinson's disease. N Engl J Med. 2023. ↩︎
Korat et al. Neurofilament light chain as a biomarker in Parkinson's disease. Nat Rev Neurol. 2022. ↩︎