Preparing for Parkinson's disease prevention trials: Current progress and future directions.

Area of Science:

• Neuroscience
• Clinical Neurology
• Biomarker Research

Background:

• Numerous clinical trials have failed to effectively delay or prevent Parkinson's disease (PD) progression.
• Key limitations include insensitive clinical scales, PD phenotype heterogeneity, and late-stage intervention targeting.

Purpose of the Study:

• To explore new strategies for preventing the onset of clinical Parkinson's disease.
• To highlight the transformative potential of recent advances in biomarker research for PD trials.

Main Methods:

• Review of limitations in conventional Parkinson's disease (PD) clinical trials.
• Analysis of emerging biomarker research (tissue, fluid, imaging) for PD.
• Examination of new frameworks for classifying synucleinopathies.

Main Results:

• Conventional scales are insufficient for early PD detection; heterogeneity complicates efficacy assessment.
• Biomarker advancements offer improved patient selection, stratification, and monitoring.
• New classification frameworks aid in distinguishing biological subtypes for targeted trials.

Conclusions:

• Preventing Parkinson's disease (PD) requires early enrollment of high-risk individuals with personalized, low-risk interventions.
• Biomarkers or sensitive clinical markers are crucial endpoints for successful prevention trials.
• Timely, ethical, and community-aligned trials necessitate early stakeholder involvement.