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The Parkinson's Progression Marker Initiative (PPMI) ? Assessment Of Clinical, Imaging And CSF PD Biomarkers

The Parkinson\'s Progression Markers Initiative
MDS: Stockholm, Sweden
Download Presentation: 729 MDS-2014-Poster-PPMI-Overview.pdf
The goal of PPMI is to identify clinical, imaging & biospecimen biomarkers of Parkinson's disease (PD) progression in subjects with manifest PD, those at risk due to genetic mutation, RBD, and/or hyposmia.

Lack of progression biomarkers has been a major roadblock to studies investigating potential disease modifying PD drugs. Lack of biomarker assessment during the prodromal period has limited understanding of the pre-motor stage of PD.

Recently diagnosed PD, healthy volunteers (HV), SWEDD subjects, prodromal PD subjects & subjects with LRRK2 or synuclein (SNCA) mutations are enrolling at 32 international clinical sites and will be followed longitudinally with comprehensive clinical, imaging and biospecimen biomarkers assessments using standardized data acquisition protocols. All study data is integrated into the PPMI study database. Access to data and biospecimens is available at www.ppmi-info.org.

The PD, HV and SWEDD cohorts have undergone baseline (n=683) and 1-year longitudinal follow-up (n=400 31Dec2013). PPMI has enrolled 423 PD (mean age 61.7, 65% Male), 196 HV (mean age 60.8, 64% Male) and 64 SWEDD (mean age 60.9, 63% Male). Duration of disease was 6.6 mo for PD and 8.0 mo for SWEDD. At baseline, the total MDS-UPDRS for PD was 32.3 compared to 4.7 for HV and 29.0 for SWEDD. Baseline MoCA, GDS, and SCOPA-AUT were 27.1, 2.3, 9.5 for PD subjects, 28.2, 1.3, 5.9 for HV and 27.1, 3.3, 13.8 for SWEDD. CSF was acquired from >97% of all subjects. Baseline CSF (pg/ml) Tau (44.7 vs 52.4), p-Tau (15.6 vs 18.3), and alpha synuclein (1847 vs 2197) were reduced in PD vs HV (p<0.01). Dopamine transporter (DAT) imaging, used as an inclusion criteria, excluded 12-15% from the PD cohort due to scans without dopaminergic deficit (SWEDD). DAT striatal SBR for PD is 1.41 vs. 2.57 for HV. Over 130,000 downloads and 25 biospecimen requests from the PPMI website have already occurred.

Baseline data from PPMI in untreated PD, HV & SWEDD cohorts demonstrate motor and non-motor deficits and reduction in CSF and imaging biomarkers in PD vs HV. Comprehensive longitudinal follow-up of the PPMI cohort is underway to characterize biomarker progression. Enrollment of prodromal PD subjects defined by hyposmia, REM behavior disorder and/or LRRK2 or SNCA mutation is underway and these cohorts will be compared to the existing PPMI subjects undergoing longitudinal follow-up.