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. 2022 Aug 16;99(7 Suppl 1):1-9.
doi: 10.1212/WNL.0000000000200789.

Planning for Prevention of Parkinson Disease: Now Is the Time

Grace F Crotty  1 , Jessi L Keavney  2 , Roy N Alcalay  2 , Kenneth Marek  2 , Gad A Marshall  2 , H Diana Rosas  2 , Michael A Schwarzschild  2
Affiliations

Planning for Prevention of Parkinson Disease: Now Is the Time

Grace F Crotty et al. Neurology. .

Abstract

Parkinson disease (PD) is a chronic progressive neurodegenerative disease with increasing worldwide prevalence. Despite many trials of neuroprotective therapies in manifest PD, no disease-modifying therapy has been established. Over the past several decades, a series of breakthroughs have identified discrete populations at substantially increased risk of developing PD. Based on this knowledge, now is the time to design and implement PD prevention trials. This endeavor builds on experience gained from early prevention trials in Alzheimer disease and Huntington disease. This article first reviews prevention trial precedents in these other neurodegenerative diseases before focusing on the critical design elements for PD prevention trials, including whom to enroll for these trials, what therapeutics to test, and how to measure outcomes in prevention trials. Our perspective reflects progress and remaining challenges that motivated a 2021 conference, "Planning for Prevention of Parkinson: A Trial Design Symposium and Workshop."

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Conflict of interest statement

J.L. Keavney reports consultation fees from ESCAPE Bio. R.N. Alcalay reports consultation fees from Avrobio, Caraway, GSK, Merck, Ono Therapeutics, and Sanofi; and research support from NIH, DoD, the Parkinson's Foundation, and The Michael. J. Fox Foundation. K. Marek reports consultation fees from Michael J Fox Foundation, GE Healthcare, Roche, UCB, Bial, Denali, Takeda, Astellas, Biohaven, Neuron23, Aprinoia, Inhibikase, Alkahest, Genentech, Invicro. Ownership in Invicro, LLC. G.A. Marshall reports research salary support for serving as site principal investigator for clinical trials sponsored by Eisai Inc., Eli Lilly and Company, and Genentech. M.A. Schwarzschild reports consultation fees for steering committee, data monitoring committee or advisory services from Denali Therapeutics, Lilly, the Parkinson Study Group (for nQ Medical, Chase Therapeutics, Partner Therapeutics, and Bial Biotech), Parkinson’s Foundation (PF), Michael J. Fox Foundation (MJFF), Sutter Health, Northwestern University, Penn State University, and Xuanwu Hospital; and research grant support from the National Institute of Health, MJFF, PF, and Farmer Family Foundation; and licensing fee royalties from Massachusetts General Hospital for adenosine 2A receptor knockout mice. G.F. Crotty and H.D. Rosas report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Pieces of the Design Puzzle for Prevention Trials in Neurodegenerative Disease: Comparing Early Progress in Selecting Design Elements for Prevention Trials Across HD, AD, and PD.
Thickness of green borders represents the relative extent to which the enclosed design element has been identified or established to enable initiation of prevention trials. For example, whom to target in HD is well established with the core feature of pathogenic expansion CAG repeats in the HD gene, possibly with prodromal features that increase likelihood of phenoconversion. In AD, all elements are sufficiently defined to have allowed numerous prevention trials. In PD, major advances in defining the genetics and prodromal state of PD have helped set the Whom piece of the trial design puzzle, and the relative safety and robustness of epidemiology (Epi)-linked risk modifiers compared to those in other neurodegenerative diseases have made them initially more attractive candidates for what to test, compared with emerging gene-targeted therapeutic strategies. How to measure prevention of PD before phenoconversion remains uncertain but is under intensive study. AD = Alzheimer disease; HD = Huntington disease; MCI = mild cognitive (cog) impairment; PD = Parkinson disease.
Figure 2
Figure 2. Roadmap to Designing PD Prevention Trials: This roadmap chronologically highlights many of the discoveries and initiatives in PD research that will lead the way to designing and implementing the first PD prevention trials.,
This roadmap chronologically highlights many of the discoveries and initiatives in PD research that will lead the way to designing and implementing the first PD prevention trials., MDS = Movement Disorder Society; PD = Parkinson disease.
See this image and copyright information in PMC

References

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