This therapeutic concept proposes low-dose LRRK2 kinase inhibition for individuals carrying LRRK2 G2019S mutations who remain pre-symptomatic for Parkinson's disease. By attenuating kinase hyperactivity before dopaminergic neuron loss becomes established, this approach aims to prevent or significantly delay clinical PD onset in this high-risk population.[1]
| Risk Category | Genetic Profile | Age Range | Biomarker Criteria |
|---|---|---|---|
| High Risk | LRRK2 G2019S homozygous | 35-50 | Normal DaTscan, normal smell |
| Moderate Risk | LRRK2 G2019S heterozygous | 45-60 | Normal DaTscan, subtle smell loss |
| Prodromal | LRRK2+ with RBD | 50-65 | Normal DaTscan, positive RBD |
| Phase | Design | Population | Primary Endpoint |
|---|---|---|---|
| II | Randomized, placebo-controlled | LRRK2 carriers, age 40-60 | Change in DaTscan at 24 months |
| III | Delayed-start | LRRK2+ prodromal | Time to clinical PD |
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