Objective: The Parkinson Progression Marker Initiative 2.0 (PPMI 2.0) is a longitudinal, observational, multi-center natural history study to assess progression of clinical features, digital outcomes, and imaging, biologic and genetic markers of Parkinson’s disease (PD) progression. The overall goal of PPMI 2.0 is to identify markers of disease progression for use in clinical trials of therapies to reduce progression of PD disability.

Background: The PPMI study has established a robust clinical and biomarker dataset and biorepository that has informed the study design of numerous planned and ongoing clinical trials in PD. PPMI 2.0 will expand and transform PPMI across the PD continuum and identify and explore the use of biomarkers to test hypotheses of the underlying molecular pathobiology of PD, enable modeling of PD progression to identify clinical and/or biologic data driven PD progression sub-sets, and inform studies testing PD therapeutics.

Method: PPMI 2.0 is a broad program, expanding the goals of the original PPMI study, that includes PPMI 2.0 Clinical, PPMI 2.0 Remote, PPMI 2.0 Digital Applications and PPMI 2.0 Online  protocols. PPMI 2.0 clinical will include the current PPMI cohorts plus approximately 900 early PD and 2000 prodromal PD participants. The prodromal cohort will be enrolled based on a staged risk paradigm with initial assessments via an online platform and remote evaluations. Those eligible would then be evaluated with DAT imaging to determine eligibility of for the densely phenotyped PPMI 2.0 Clinical five year follow-up.

Results: PPMI 2.0 Clinical will begin enrollment in 2020.  Data supporting PPMI 2.0 comes from Fox Insight (FI), the PPMI, the Parkinson Associated Risk Syndrome (PARS) and RBD studies (Jennings et al. 2017J, Iranzo et al. 2017).  Data from PPMI, PARS, and RBD studies suggests that among subjects identified with either PSG-documented RBD or hyposmia (defined as <10% of age and gender UPSIT) who have DAT deficit, the risk of conversion to motor parkinsonism within 3-5 years is approximately 30%.

Conclusion: PPMI 2.0 will expand the existing data set and biorepository already available from PPMI and extend the study throughout the PD continuum with a focus on prodromal PD. This strategy has the potential to establish a framework for developing a prodromal PD cohort and to identify meaningful clinical and biomarker outcomes that could accelerate clinical trials of both manifest and prodromal PD.

References: Jennings et al, JAMA Neurol. 2017;74(8):933-940 Iranzo et al. Ann Neurol 2017; 82(3): 419-28

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinson-progression-marker-initiative-2-0-new-science-new-cohorts/