Finding useful biomarkers for Parkinson's disease

Alice S Chen-Plotkin¹, Roger Albin^{2

3}, Roy Alcalay⁴, Debra Babcock⁵, Vikram Bajaj⁶, Dubois Bowman⁷, Alex Buko⁸, Jesse Cedarbaum⁹, Daniel Chelsky¹⁰, Mark R Cookson¹¹, Ted M Dawson¹², Richard Dewey¹³, Tatiana Foroud¹⁴, Mark Frasier¹⁵, Dwight German¹⁶, Katrina Gwinn⁵, Xuemei Huang¹⁷, Catherine Kopil¹⁵, Thomas Kremer¹⁸, Shirley Lasch¹⁹, Ken Marek¹⁹, Jarrod A Marto^{20

21

22}, Kalpana Merchant²³, Brit Mollenhauer^{24

25}, Anna Naito¹⁵, Judith Potashkin²⁶, Alyssa Reimer¹⁵, Liana S Rosenthal²⁷, Rachel Saunders-Pullman²⁸, Clemens R Scherzer²⁹, Todd Sherer¹⁵, Andrew Singleton³⁰, Margaret Sutherland⁵, Ines Thiele³¹, Marcel van der Brug³², Kendall Van Keuren-Jensen³³, David Vaillancourt³⁴, David Walt²², Andrew West³⁵, Jing Zhang³⁶

Affiliations

¹ Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. chenplot@pennmedicine.upenn.edu.
² Neurology Service and GRECC, VAAHS, Ann Arbor, MI 48105, USA.
³ Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
⁵ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20824, USA.
⁶ Verily/Google Life Sciences, South San Francisco, CA 94080, USA.
⁷ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
⁸ Human Metabolome Technology-America, Boston, MA 02134, USA.
⁹ Biogen, Cambridge, MA 02142, USA.
¹⁰ Caprion Biosciences, Montreal, Quebec H2X 3Y7, Canada.
¹¹ Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, MD 20892, USA.
¹² Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹³ Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹⁴ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁵ The Michael J. Fox Foundation for Parkinson's Research, New York, NY 10163, USA.
¹⁶ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹⁷ Department of Neurology, Penn State University-Hershey Medical Center, Hershey, PA 17033, USA.
¹⁸ Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
¹⁹ Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.
²⁰ Departments of Cancer Biology and Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
²¹ Blais Proteomics Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
²² Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
²³ Chaperone Therapeutics, Portland, OR 97229, USA.
²⁴ Paracelsus-Elena-Klinik, 34128 Kassel, Germany.
²⁵ University Medical Center, 37075 Goettingen, Germany.
²⁶ Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, IL 60064, USA.
²⁷ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
²⁸ Department of Neurology, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, NY 10003, USA.
²⁹ Center for Advanced Parkinson's Disease Research and Precision Neurology Program, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
³⁰ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
³¹ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg.
³² Genentech, San Francisco, CA 94080, USA.
³³ Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
³⁴ Department of Applied Physiology, Biomedical Engineering, and Neurology, University of Florida, Gainesville, FL 32611, USA.
³⁵ Department of Neurology, University of Alabama, Birmingham, AL 35233, USA.
³⁶ Department of Pathology, University of Washington, Seattle, WA 98195, USA.

PMID: 30111645
PMCID: PMC6097233
DOI: 10.1126/scitranslmed.aam6003

Review

Finding useful biomarkers for Parkinson's disease

Alice S Chen-Plotkin et al. Sci Transl Med. 2018.

. 2018 Aug 15;10(454):eaam6003.

doi: 10.1126/scitranslmed.aam6003.

Authors

Affiliations

¹ Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. chenplot@pennmedicine.upenn.edu.
² Neurology Service and GRECC, VAAHS, Ann Arbor, MI 48105, USA.
³ Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
⁵ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20824, USA.
⁶ Verily/Google Life Sciences, South San Francisco, CA 94080, USA.
⁷ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
⁸ Human Metabolome Technology-America, Boston, MA 02134, USA.
⁹ Biogen, Cambridge, MA 02142, USA.
¹⁰ Caprion Biosciences, Montreal, Quebec H2X 3Y7, Canada.
¹¹ Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, MD 20892, USA.
¹² Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹³ Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹⁴ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁵ The Michael J. Fox Foundation for Parkinson's Research, New York, NY 10163, USA.
¹⁶ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹⁷ Department of Neurology, Penn State University-Hershey Medical Center, Hershey, PA 17033, USA.
¹⁸ Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
¹⁹ Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.
²⁰ Departments of Cancer Biology and Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
²¹ Blais Proteomics Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
²² Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
²³ Chaperone Therapeutics, Portland, OR 97229, USA.
²⁴ Paracelsus-Elena-Klinik, 34128 Kassel, Germany.
²⁵ University Medical Center, 37075 Goettingen, Germany.
²⁶ Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, IL 60064, USA.
²⁷ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
²⁸ Department of Neurology, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, NY 10003, USA.
²⁹ Center for Advanced Parkinson's Disease Research and Precision Neurology Program, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
³⁰ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
³¹ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg.
³² Genentech, San Francisco, CA 94080, USA.
³³ Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
³⁴ Department of Applied Physiology, Biomedical Engineering, and Neurology, University of Florida, Gainesville, FL 32611, USA.
³⁵ Department of Neurology, University of Alabama, Birmingham, AL 35233, USA.
³⁶ Department of Pathology, University of Washington, Seattle, WA 98195, USA.

PMID: 30111645
PMCID: PMC6097233
DOI: 10.1126/scitranslmed.aam6003

Abstract

The recent advent of an "ecosystem" of shared biofluid sample biorepositories and data sets will focus biomarker efforts in Parkinson's disease, boosting the therapeutic development pipeline and enabling translation with real-world impact.

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Figures

**Figure 1**
Means and standard errors of the mean (SEM) for scores on the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)-III for PPMI cohort participants. Pink=Healthy controls (HC). Yellow=subjects without evidence of dopaminergic deficit (SWEDD). Parkinson’s Disease patients stratified by tertile of MDS-UPDRS-III score are shown for the lowest tertile (blue), middle tertile (black), and highest tertile (red).

**Figure 2**
A pipeline for Parkinson’s Disease biomarker discovery and development.

See this image and copyright information in PMC

References

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1. Parkinson Study Group SURE-PD Investigators. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014;71:141–150. - PMC - PubMed
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Finding useful biomarkers for Parkinson's disease

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Finding useful biomarkers for Parkinson's disease

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