The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

the Parkinson's Progression Markers Initiative

doi:10.1002/acn3.644

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

the Parkinson's Progression Markers Initiative

Vagelos College of Physicians and Surgeons

Research output: Contribution to journal › Article › peer-review

328 Citations (Scopus)

Abstract

Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

Original language	English
Pages (from-to)	1460-1477
Number of pages	18
Journal	Annals of Clinical and Translational Neurology
Volume	5
Issue number	12
DOIs	https://doi.org/10.1002/acn3.644
Publication status	Published - Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

Funding

PPMI is sponsored by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbvie, Allergan, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol-Myers Squibb Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer, Sanofi Genzyme, Servier, Takeda, Teva, and UCB. Kenneth Marek receives funding from the The Michael J. Fox Foundation, the US Department of Defense and is employed by Invicro and has received consultant fees from Pfizer, GE Healthcare, Lilly, BMS, Piramal, Biogen, Prothena, Roche, Neuropore, US Worldmeds, Neu-rophage, UCB, Oxford Biomedica, Lysosomal Therapetic, Inc, Neuroderm, Denali and the Michael J. Fox Foundation. Sohini Chowdhury is employed by The Michael J. Fox Foundation. Shirley Lasch is employed by Molecular NeuroImaging, LLC. Christopher S. Coffey served as a consultant receiving consulting fees from The Michael J. Fox Foundation for Parkinson’s Research; Received research funding from NINDS, NHLBI, and The Michael J. Fox Foundation for Parkinson’s Research. Chelsea Caspell-Garcia served as a consultant receiving consulting fees from The Michael J. Fox Foundation for Parkinson’s Research; Received research funding from The Michael J. Fox Foundation for Parkinson’s Research. Danna Jennings is an employee of Eli Lilly. Caroline M Tanner is an employee of the San Francisco Veterans Affairs Medical Center and the University of California – San Francisco. She receives grants from the Michael J. Fox Foundation, the Parkinson’s Disease Foundation, the Department of Defense, Sage Bionetworks and the National Institutes of Health, compensation for serving on Data Monitoring Committees from Biotie Therapeutics, Voyager Therapeutics and Intec Pharma and personal fees for consulting from Neurocrine Biosciences, Adamas Pharmaceuticals, Photopharmics and 23andMe. Tanya Simuni has served as a consultant and received consulting fees from Acadia, Abbvie, Allergan, Anavex, Avid, GE Medical, Eli Lilly and Company, Harbor, Ibsen, IMPAX, Lundbeck, Merz, Inc., the National Parkinson Foundation, Navidea, Pfizer, TEVA Pharmaceuticals, UCB Pharma, Voyager, US World Meds, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni has served as a speaker and received an honorarium from Acadia, IMPAX, Lundbeck, TEVA Pharmaceuticals, and UCB Pharma; Dr Simuni is on the Scientific advisory board for Anavex, Sanofi, MJFF. Dr. Simuni sits on the Advisory Board for IMPAX; Dr. Simuni has received research funding from the NINDS, MJFF, NPF, TEVA Pharmaceuticals, Auspex, Biotie, Civitas, Acorda, Lund-beck, Neuroderm, NINDS, National Institutes of Health, Northwestern Foundation, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni received funding support for educational programs from GE Medical, TEVA, and Lundbeck. Daniel Weintraub has received research funding or support from Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health (NINDS), Novartis Pharmaceuticals, Department of Veterans Affairs, Avid Radiopharmaceuticals, Alzheimer’s Disease Cooperative Study, and the International Parkinson and Movement Disorder Society; honoraria for consultancy from Acadia, Biogen, Biotie (Acorda), Bracket, Clintrex LLC, Eisai Inc., Eli Lilly, Lundbeck, Roche, Takeda, UCB, and the CHDI Foundation; license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS; royalties from Wolters Kluweland; and fees for legal consultation for lawsuits related to medication prescribing in patients with Parkinson’s disease. Lana M. Chahine receives support from the Michael J Fox Foundation and receives royalties from Wolters Klu-wel (for book authorship) John Trojanowski may accrue revenue in the future on patents submitted by the University of Pennsylvania wherein he is co-inventor and he received revenue from the sale of Avid to Eli Lily as coinventor on imaging related patents submitted by the University of Pennsylvania. Karl Kieburtz has served as a consultant and received consulting fees from: Acorda, Astellas Pharma, AstraZeneca, BioMarin Pharmaceutica, Biotie, Britannia, CHDI, Clearpoint Strategy Group, Clin-trex, Corium International, Cynapsus, Forward Pharma, Genzyme, INC Research, Intec, Lundbeck, Medivation, Melior Discovery, Neurocrine, Neuroderm, Neurmedix, Orion Pharma, Otsuka, Pfizer, Pharma2B, Prana Biotechnology, Prothena/Neotope/Elan Pharmaceutical, Raptor Pharmaceuticals, Remedy Pharmaceuticals, Roche/Genen-tech, Sage Bionetworks, Sanofi, Serina, Sunovion, Synag-ile, Titan, Upsher-Smith, US WorldMeds, Vaccinex, Vertex Pharmaceuticals, Voyager, and Weston Brain Institute. Dr. Kieburtz has received funding from National Institutes of Health (NINDS), The Michael J Fox Foundation, and Teva. Kathleen L Poston receives funding from The Michael J. Fox Foundation and the National Institutes of Health. Andrew Siderowf has been a full time employee of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Co, in the past 12 months. Thomas Comery is employed by Pfizer, Inc. Brit Mollen-hauer is employed by Parcacelsus Kliniken Germany and the University Medical Center Goettingen; BM has received independent research grants from TEVA-Pharma, Desitin, Boehringer Ingelheim, GE Healthcare and honoraria for consultancy from Bayer Schering Pharma AG, Roche, AbbVie, TEVA-Pharma, Biogen and for presentations from GlaxoSmithKline, Orion Pharma, TEVA-Pharma and travel costs from TEVA-Pharma. BM is member of the executive steering committee of the Parkinson Progression Marker Initiative and the Systemic Synuclein Sampling Study of the Michael J. Fox Foundation for Parkinson’s Research and has received grants from the BMBF, EU, Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, Michael J. Fox Foundation for Parkinson’s Research, Stifterverband fu€r die deutsche Wissenschaft, and has scientific collaborations with Roche, Bristol Myers Squibb, Ely Lilly, Covance and Biogen. Douglas Galasko receives research funding from NIH, Michael J. Fox Foundation, and Eli Lilly and Esai. He is a paid Editor for Alzheimer’s Research and Therapy. He is a consultant for vTv Therapeutics and serves on a DSMB for Prothena. Tatiana Foroud receives funding from the National Institutes of Health (NIH), The Michael J. Fox Foundation, the US Department of Defense. Dr. Foroud has received funding from The Michael J. Fox Foundation, the NIH, San Diego State University, The University of Texas at Austin, and Waggoner Center for Alcohol/Addiction Research. Vanessa Arnedo is employed by The Michael J. Fox Foundation. Mark Frasier is employed by The Michael J. Fox Foundation. Todd Sherer is employed by The Michael J. Fox Foundation. PPMI is sponsored by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbvie, Allergan, Avid Radiopharmaceuticals, Biogen, Bristol-Myers Squibb, BioLegend, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genen-tech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer, Sanofi Genzyme, Servier, Takeda, Teva, and UCB.

Funders	Funder number
Alzheimer’s Disease Cooperative Study
Biotie Therapeutics
Eli Lilly & Co.
F. Hoffman-La Roche, Ltd.
GE Medical
MesoScale
Michael J Fox Foundation
Northwestern Foundation
Orion Pharma
Parkinson Fonds Deutschland
Piramal
Sage Bionetworks
Stifterverband fu€r die deutsche Wissenschaft
TEVA-Pharma
University Medical Center Goettingen
Waggoner Center for Alcohol/Addiction Research
National Institutes of Health
U.S. Department of Defense
National Heart, Lung, and Blood Institute
National Institute of Neurological Disorders and Stroke
Michael J. Fox Foundation for Parkinson's Research
Boehringer Ingelheim
National Park Foundation
Eli Lilly and Company
Pfizer
Merck
Biogen
North Carolina GlaxoSmithKline Foundation
CHDI Foundation
Teva Pharmaceutical Industries
AbbVie
GE Healthcare
University of Pennsylvania
Takeda Pharmaceuticals U.S.A.
Allergan
Bristol-Myers Squibb Canada
Novartis Pharmaceuticals Corporation
University of Texas at Austin
Parkinson’s Disease Foundation of India
UCB
School of Public Health, University of California Berkeley
Sanofi Genzyme
ACADIA Pharmaceuticals
Avid Radiopharmaceuticals
Roche Diagnostics
European Commission
Bundesministerium für Bildung und Forschung
Eisai Incorporated
Bayer Schering
Servier
H. Lundbeck A/S
Deutsche Parkinson Vereinigung
Desitin Arzneimittel

ASJC Scopus Subject Areas

General Neuroscience
Clinical Neurology

Access to Document

10.1002/acn3.644

Cite this

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title = "The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort",

abstract = "Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.",

author = "{the Parkinson's Progression Markers Initiative} and Kenneth Marek and Sohini Chowdhury and Andrew Siderowf and Shirley Lasch and Coffey, {Christopher S.} and Chelsea Caspell-Garcia and Tanya Simuni and Danna Jennings and Tanner, {Caroline M.} and Trojanowski, {John Q.} and Shaw, {Leslie M.} and John Seibyl and Norbert Schuff and Andrew Singleton and Karl Kieburtz and Toga, {Arthur W.} and Brit Mollenhauer and Doug Galasko and Chahine, {Lana M.} and Daniel Weintraub and Tatiana Foroud and Duygu Tosun-Turgut and Kathleen Poston and Vanessa Arnedo and Mark Frasier and Todd Sherer and Susan Bressman and M. Merchant and Werner Poewe and Catherine Kopil and Anna Naito and Ray Dorsey and Cynthia Casaceli and Nichole Daegele and Justin Albani and Liz Uribe and Eric Foster and Jeff Long and Nick Seedorff and Karen Crawford and Danielle Smith and Paola Casalin and Giulia Malferrari and Cheryl Halter and Laura Heathers and David Russell and Stewart Factor and Penelope Hogarth and Amy Amara and Karen Marder",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.",

year = "2018",

month = dec,

doi = "10.1002/acn3.644",

language = "English",

volume = "5",

pages = "1460--1477",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

publisher = "John Wiley and Sons Ltd",

number = "12",

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T1 - The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

AU - the Parkinson's Progression Markers Initiative

AU - Marek, Kenneth

AU - Chowdhury, Sohini

AU - Siderowf, Andrew

AU - Lasch, Shirley

AU - Coffey, Christopher S.

AU - Caspell-Garcia, Chelsea

AU - Simuni, Tanya

AU - Jennings, Danna

AU - Tanner, Caroline M.

AU - Trojanowski, John Q.

AU - Shaw, Leslie M.

AU - Seibyl, John

AU - Schuff, Norbert

AU - Singleton, Andrew

AU - Kieburtz, Karl

AU - Toga, Arthur W.

AU - Mollenhauer, Brit

AU - Galasko, Doug

AU - Chahine, Lana M.

AU - Weintraub, Daniel

AU - Foroud, Tatiana

AU - Tosun-Turgut, Duygu

AU - Poston, Kathleen

AU - Arnedo, Vanessa

AU - Frasier, Mark

AU - Sherer, Todd

AU - Bressman, Susan

AU - Merchant, M.

AU - Poewe, Werner

AU - Kopil, Catherine

AU - Naito, Anna

AU - Dorsey, Ray

AU - Casaceli, Cynthia

AU - Daegele, Nichole

AU - Albani, Justin

AU - Uribe, Liz

AU - Foster, Eric

AU - Long, Jeff

AU - Seedorff, Nick

AU - Crawford, Karen

AU - Smith, Danielle

AU - Casalin, Paola

AU - Malferrari, Giulia

AU - Halter, Cheryl

AU - Heathers, Laura

AU - Russell, David

AU - Factor, Stewart

AU - Hogarth, Penelope

AU - Amara, Amy

AU - Marder, Karen

PY - 2018/12

Y1 - 2018/12

N2 - Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

AB - Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

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The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Abstract

Bibliographical note

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