Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Katrina Gwinn¹, Karen K David¹, Christine Swanson-Fischer¹, Roger Albin², Coryse St Hillaire-Clarke³, Beth-Anne Sieber¹, Codrin Lungu¹, F DuBois Bowman⁴, Roy N Alcalay⁵, Debra Babcock¹, Ted M Dawson⁶, Richard B Dewey Jr⁷, Tatiana Foroud⁸, Dwight German⁹, Xuemei Huang¹⁰, Vlad Petyuk¹¹, Judith A Potashkin¹², Rachel Saunders-Pullman¹³, Margaret Sutherland¹, David R Walt¹⁴, Andrew B West¹⁵, Jing Zhang¹⁶, Alice Chen-Plotkin¹⁷, Clemens R Scherzer¹⁸, David E Vaillancourt¹⁹, Liana S Rosenthal²⁰

Affiliations

¹ National Institute of Neurological Disorders & Stroke, National Institutes of Health, Bethesda, MD, USA.
² Neurology Service & GRECC, VAAAHS, UM Udall Center, University of Michigan, Ann Arbor, MI, USA.
³ National Institute on Aging, NIH, Bethesda, MD, USA.
⁴ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁵ Department of Neurology, Columbia University, New York, NY, USA.
⁶ Neuroregeneration & Stem Cell Programs, Institute for Cell Engineering, Solomon H Snyder Department of Neuroscience, Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁸ Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁹ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁰ Department of Neurology, Penn State Hershey Medical Center, Hershey, PA, USA.
¹¹ Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
¹² Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine & Science, North Chicago, IL, USA.
¹³ Department of Neurology, Mount Sinai Beth Israel & Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Department of Chemistry, Tufts University, Medford, MA, USA.
¹⁵ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁷ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁸ Department of Neurology, Harvard Medical School, Brigham & Women's Hospital, Cambridge, MA, USA.
¹⁹ Departments of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA.
²⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 28644039
PMCID: PMC5619098
DOI: 10.2217/bmm-2016-0370

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Katrina Gwinn et al. Biomark Med. 2017 May.

. 2017 May;11(6):451-473.

doi: 10.2217/bmm-2016-0370. Epub 2017 Jun 23.

Authors

Affiliations

¹ National Institute of Neurological Disorders & Stroke, National Institutes of Health, Bethesda, MD, USA.
² Neurology Service & GRECC, VAAAHS, UM Udall Center, University of Michigan, Ann Arbor, MI, USA.
³ National Institute on Aging, NIH, Bethesda, MD, USA.
⁴ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁵ Department of Neurology, Columbia University, New York, NY, USA.
⁶ Neuroregeneration & Stem Cell Programs, Institute for Cell Engineering, Solomon H Snyder Department of Neuroscience, Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁸ Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁹ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁰ Department of Neurology, Penn State Hershey Medical Center, Hershey, PA, USA.
¹¹ Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
¹² Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine & Science, North Chicago, IL, USA.
¹³ Department of Neurology, Mount Sinai Beth Israel & Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Department of Chemistry, Tufts University, Medford, MA, USA.
¹⁵ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁷ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁸ Department of Neurology, Harvard Medical School, Brigham & Women's Hospital, Cambridge, MA, USA.
¹⁹ Departments of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA.
²⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 28644039
PMCID: PMC5619098
DOI: 10.2217/bmm-2016-0370

Abstract

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset.

Keywords: NINDS; PDBP; Parkinson's disease; biomarkers.

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Conflict of interest statement

Financial & competing interests disclosure

K Gwinn, K David, C Swanson-Fischer, C St Hillaire-Clarke, Beth-Anne Sieber, C Lungu, D Babcock and M Sutherland are employees of the NIH, which funded this project. R Albin is supported by R56NS082941, P50NS091856 and a grant from the Michael J Fox Foundation. C Scherzer is supported by NIH grants U01 NS082157, U01NS095736, U01 NS082080, U01NS100603; US Department of Defense grant W81XWH-15–10007; the Michael J Fox Foundation and the MEMO Hoffman Foundation. D Vaillancourt is supported by grants from NIH, Bachmann-Strauss and Tyler's Hope Foundation during the conduct of the study, and received personal honoraria from NIH, National Parkinson's Foundation, UT Southwestern Medical Center and Northwestern University unrelated to the submitted work. A Chen-Plotkin is supported by NIH-NINDS (P50 NS053488 and UO1 NS082134), the Burroughs Wellcome Fund, the Benaroya Fund and the Pechenik Montague Award Fund. F DuBois Bowman receives funding from the National Institutes of Health and the Michael J Fox Foundation. R Alcalay is supported by the Parkinson's Disease Foundation, the National Institutes of Health (K02NS080915), the Smart Foundation and the Michael J Fox Foundation. He received consultation fees from Genzyme/Sanofi and Prophase. TM Dawson is supported by NIH/NINDS P50NS038377, NIH/NINDS U01NS082133 and NIH/NINDS U01NOS097049. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. R Dewey Jr is supported by NINDS U01-NS082148. Dewey reports to have received personal fees from UCB, Lundbeck, US WorldMeds, Merz, Impax, Acorda, Acadia and Teva, and grants from University of Texas System, outside the submitted work. T Foroud is supported by NIH/NINDS U24 NS095871. D German is supported by NIH/NINDS U01 NS082148. X Huang is supported by NIH/NINDS U01 NS082151. V Petyuk is supported for this project by NIH/NINDS U18 NS082140. JA Potashkin is supported by the US Army Medical Research and Materiel Command under awards W81XWH-09–0708 and W81XWH13–1–0025 and NIH/NINDS U01 NS097037. R Saunders-Pullman is supported by NIH/NINDS U01 NS094148, the Bigglesworth Family Foundation and the Gaucher Generations Program from Genzyme-Sanofi. D Walt is a member of the Boards of Directors of Cerulean, Quanterix, Exicure and Ultivue Inc. AB West is supported by NIH/NINDS R01 NS064934, U01 NS097028, R33 NS097643 and P20 NS092530. L Rosenthal is supported by NIH/NINDS P50NS038377, NIH/NINDS U01NS082133 and NIH/NINDS U01NOS097049. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b> — **Figure 1.**. **The typical biomarker development pipeline.**
The typical pipeline includes significant basic research in association with well-characterized clinical cohorts. Any biomarkers discovered and replicated, must be validated and shown to qualify as biomarkers. Reproduced from [12].

See this image and copyright information in PMC

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Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

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Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

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