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Precision medicine for disease modification in Parkinson disease

Nature Reviews Neurology volume 13, pages 119–126 (2017)Cite this article

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Parkinson disease (PD) is a complex disorder that encompasses various clinical, epidemiological and genetic subtypes. Approaching PD as a single diagnostic entity has been effective for developing symptomatic therapies but ineffective when targeting neuroprotection or attempting disease modification. The growing number of failed attempts to establish neuroprotective therapies for PD might in part be explained by a simplistic single-target approach to drug development. Here, we argue that more attention should be paid to the symptomatic and pathological differences between patients. We propose that patients belong to distinct nodes or clusters, which are defined by clinical, pathological, genetic and molecular features of the disease. We conclude that the adoption of precision medicine in PD will require a revision of biomarker development efforts, with the ultimate goal of testing putative disease-modifying interventions in well-defined disease subgroups, as opposed to the large and heterogeneous disease populations that are typically recruited into clinical trials.

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Figure 1: Diagnostic tiers of Parkinson disease as single disease.
Figure 2: Precision medicine based on a network approach.
Figure 3: Biaxial clinical and pathophysiological classification of PD needed for precision medicine.

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Author information

Authors and Affiliations

  1. Department of Neurology, James J and Joan A Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson Street, Suite 2300, Cincinnati, 45219, Ohio, USA

    Alberto J. Espay

  2. The Laboratory of Translational Parkinson's Disease Research and The Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue N.E., Grand Rapids, 49503, Michigan, USA

    Patrik Brundin

  3. The Morton and Gloria Shulman Movement Disorders Clinic and The Edmond J. Safra Program in Parkinson's Disease, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, M5T 2S8, Ontario, Canada

    Anthony E. Lang

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Contributions

A.J.E. developed the concept, researched data for the article and wrote the article. P.B. and A.E.L. made substantial contributions to discussions of the content and reviewed and edited the manuscript. All authors approved the final version of this manuscript.

Corresponding author

Correspondence to Alberto J. Espay.

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Competing interests

A.J.E. has received grant support from Great Lakes Neurotechnologies; personal compensation as a consultant/scientific advisory board member for Abbvie, TEVA, Impax, Merz, Acadia, Cynapsus, Lundbeck, and USWorldMeds; royalties from Lippincott Williams & Wilkins and Cambridge University Press; and honoraria from Abbvie, USWorldMeds, Lundbeck, and Acadia. P.B. has served and received personal compensation as a consultant/scientific advisory board member for Capital Technologies, Cure Parkinson's Trust, Renovo Neural, Roche Holding, Teva, Lundbeck A/S and AbbVie; holds equity interest in Acousort, and ParkCell; received honoraria or sponsored/reimbursed travel from American Academy of Neurology, FCB Health, Fondazione Cariplo, Fonds National De la Recherche Luxembourg, Innsbruck Synuclein Symposium, Knut och Alice Wallenbergs Stiftelse and Prothena Corporation. A.E.L. has served as an adviser for Abbvie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec, Boerhinger-Ingelheim, Ceregene, Lilly, Medtronic, Merck, Novartis, NeuroPhage Pharmaceuticals, Teva and UCB; received honoraria from Medtronic, Teva, UCB, AbbVie; received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry.

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Glossary

Classic PD

Clinical presentation of asymmetric bradykinesia with rigidity and resting hand or foot tremor, later accompanied by impairments in gait or postural balance, but in the absence of any other neurological abnormalities.

Neurogenic orthostatic hypotension

Recurrent orthostatic fall in systolic blood pressure of ≥20 mmHg or diastolic pressure of ≥10 mmHg within 3 min after standing up, due to abnormalities in the reflexive regulation of the circulation by the sympathetic noradrenergic system.

Target engagement

The interaction between a drug and its target. PET imaging can be used to measure target engagement during clinical trials.

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Espay, A., Brundin, P. & Lang, A. Precision medicine for disease modification in Parkinson disease. Nat Rev Neurol 13, 119–126 (2017). https://doi.org/10.1038/nrneurol.2016.196

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