Objective: The overall objective of the Path to Prevention (P2P) initiative is to identify clinical, imaging, and biologic markers of progression during the prodromal phase of Parkinson’s disease (PD) to inform early intervention clinical trials of disease-modifying therapies.

Background: Recent understanding of both the early non-motor manifestations and the molecular genetics of PD have provided several specific strategies to identify individuals without typical PD motor symptoms, but at increased risk to develop PD. DAT imaging has been utilized to identify individuals with prodromal features of PD at high risk of conversion to motor Parkinsonism.

Method: P2P will evaluate study participants utilizing a staged risk assessment paradigm beginning with P2P Remote, utilizing Fox Insight (FI)  to identify participants at risk based on self-reported outcomes from online motor and non-motor questionnaires, or by known risk due to RBD or genetic mutation, followed by remote assessments of olfaction, genetic risk, and digital motor function.  Select participants would be eligible to enroll in P2P Clinic in which their risk would be further assessed with DAT imaging. Approximately 1200 participants with DAT deficit will be eligible to enroll in a longitudinal, comprehensive assessment of motor, non-motor, imaging, and biologic testing for 3-5 years to assess phenoconversion and biomarker progression.

Results: P2P is expected to begin enrollment in 2019.  Data supporting the P2P initiative comes from FI, PPMI and the PARS study.  Approximately 31,000 (PD and non-PD) participants are enrolled in FI and the study program has effectively collected participant’s reported outcomes that allow identification of individuals without PD who endorse non-motor symptoms including constipation (~30%), dream enactment (~16%), and  reduced taste/smell (~8%). Data from PPMI and PARS suggests that among subjects identified with either  RBD or hyposmia,  who have DAT deficit, the risk of conversion to motor parkinsonism within 3 years is approximately 30%.

Conclusion: It is feasible to develop a comprehensive prodromal PD initiative to identify participants at risk from the community using a staged remote, followed by in clinic, assessment paradigm.  This strategy has the potential to establish a framework for developing a prodromal PD cohort and to identify clinical and biomarker outcomes that could accelerate clinical trials of prodromal PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/path-to-prevention-p2p-developing-a-prodromal-pd-progression-biomarker-program/