Professor Simon Lewis summarises a Clinical Breakthrough presentation, first delivered at the International Parkinson and Movement Disorder Society meeting (Seoul, 2026), describing early results from an investigator‑initiated, philanthropically funded (Parkinson’s UK) trial of a brain‑penetrant small‑molecule provided by Syntara. He explains why isolated REM sleep behaviour disorder (iRBD), where people act out dreams, is a powerful predictor of Parkinson’s and related diseases, often years before diagnosis, allowing a crucial window for prevention.
Professor Lewis outlines the rationale that neuroinflammation may drive neurodegeneration and highlights two inflammation‑related enzymes acting in the brain (monoamine oxidase in glial cells and SSAO/VAP‑1 in the vascular endothelium) that might be driving this process. He also describes prior PET imaging showing inflammation in Parkinson’s and critically in prodromal iRBD patients where neuroinflammation predicts future dopamine cell loss.
In the double‑blind study, 41 iRBD participants with PET‑evident inflammation were randomised 3:1 to drug or placebo for 12 weeks, with follow‑up to 24 weeks. The drug was well tolerated, with no serious adverse events and 39/41 had positive alpha‑synuclein CSF tests. Primary imaging outcomes showed a statistically significant reduction in neuroinflammation in most treated participants, with no placebo change. IN addition, physical rating scales also favoured the drug at 24 weeks, suggesting more than just a symptomatic benefit as the drug was only taken for the first 12 weeks of the study. Prof Lewis argues that these findings justify larger, longer trials in both prodromal and early‑diagnosis cohorts.
Volunteer for our research here: https://bit.ly/PDRC_EOI