Arvinas presented Phase 1 data showing oral PROTAC ARV‑102 achieved approximately ≥50% reduction of LRRK2 protein in cerebrospinal fluid after 14 days and maintained reduction through 28 days in Parkinson’s disease patients. The randomized, multiple‑dose study measured central target engagement and downstream biomarker changes tied to endolysosomal and neuroinflammatory pathways. The lead sentence: ARV‑102 demonstrated central nervous system target degradation, providing early proof‑of‑concept for a brain‑penetrant degrader. Dose‑dependent CSF exposure and consistent LRRK2 depletion across dose cohorts supported the conclusion that the PROTAC reached the brain and degraded the intended target. Safety was acceptable across evaluated doses. Investigators and Arvinas framed the results as supportive of further development across LRRK2‑driven neurodegenerative indications, including progressive supranuclear palsy. The data advance the therapeutic protein‑degradation field by showing CSF biomarker modulation for a small‑molecule degrader, addressing a key challenge for neurodegenerative drug development: delivering mechanism‑based molecules across the blood‑brain barrier and achieving central biochemical effects.