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How PPMI Enabled the First Interventional Platform Trial to Test Therapies in Participants With Early-Stage Neuronal Alpha-Synuclein Disease
Journal article   Peer reviewed

How PPMI Enabled the First Interventional Platform Trial to Test Therapies in Participants With Early-Stage Neuronal Alpha-Synuclein Disease

Tanya Simuni, Christopher S Coffey, Catherine M Kopil, Cora Allen-Savietta, Barbara Wendelberger, Amy Crawford, Ruth B Schneider, Andrew Siderowf, Karl Kieburtz, Caroline M Tanner, …
Annals of neurology
05/07/2026
DOI: 10.1002/ana.78250
PMID: 42095573

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Abstract

The Path to Prevention (P2P) platform trial is a multicenter, multi-regimen, proof of concept, phase 2A, randomized clinical trial evaluating the safety and early efficacy of investigational products for the treatment of early-stage Neuronal Alpha-Synuclein disease (NSD) populations. The P2P trial is nested within the Parkinson's Progression Markers Initiative (PPMI), which means that its conceptualization, design, and implementation are based on learnings from the PPMI study. P2P will recruit eligible participants from the PPMI cohort. P2P will also leverage PPMI infrastructure including PPMI study sites and PPMI study cores including the site management, data management, biorepository, imaging, statistical, and data science cores for study execution. This paper reviews the conceptual design of P2P focusing on its relationship with PPMI to demonstrate how the connectivity between PPMI and P2P is essential for the success of the P2P study. P2P is an important step forward in clarifying the clinical trial design and regulatory path for interventions in the early-stage NSD population. ANN NEUROL 2026.

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