Summary
As mentioned in the Introduction,3 we provide a framework for addressing the critical next steps in designing trials to prevent PD by addressing the following questions: Who (should be enrolled)? What (to test)? and How (to measure prevention)? complemented ultimately by When during the disease (should we start these trials)?
Original Article
Path to Parkinson Disease Prevention. Conclusion and Outlook
Neurology
Daniela Berg, Grace F. Crotty, Jessi L. Keavney, Michael A. Schwarzschild, Tanya Simuni, Caroline Tanner
Abstract
Tremendous progress in our understanding of the pathophysiology and clinical manifestations of the prodromal phase of Parkinson disease (PD) offers a unique opportunity to start therapeutic interventions as early as possible to slow or even stop the progression to clinically manifest motor PD. A Parkinson's Prevention Conference, “Planning for Prevention of Parkinson's: A trial design symposium and workshop” was convened to discuss all issues that need to be addressed before the launch of the first PD prevention study. In this review, we summarize the major opportunities and challenges in designing prevention trials in PD, organized by the following critical trial design questions: Who (should be enrolled)? What (to test)? How (to measure prevention)? and the pivotal question, When during the prodromal disease (should we start these trials)? We outline the implications of these questions and their meaning for a responsible, sustainable, and fruitful further planning for prevention trials. Despite the great progress that has been made, it needs to be acknowledged that several queries remain to be carefully considered and addressed because prevention trials are being planned and become a reality.
The past 3 decades have revolutionized our understanding of the early years of Parkinson disease (PD). The hypothesis that a long prodromal phase precedes the clinical diagnosis of PD was proposed in Neurology® as far back as 1991.1 Thirty years later, evidence supporting both the existence of prodromal nonmotor markers, reflecting underlying peripheral nervous system and CNS pathology, and of subtle motor signs of early nigrostriatal system involvement is well established. In parallel with advancements in better understanding of the disease biology and development of biologically targeted therapeutics, it is imperative to consider starting therapy in the prodromal phase to slow or even stop the progression to clinically manifest motor PD. Therapeutic trials targeting the prodromal population are being implemented in other neurodegenerative diseases, specifically Alzheimer disease, and can provide insights to the complexity and path forward.2 Reflecting insights shared throughout this Neurology supplement, Planning for the Prevention of Parkinson Disease: Perspectives on Trial Design, we believe that the field has accumulated sufficient critical knowledge to start addressing the quintessential questions of designing interventional studies in individuals at risk for developing PD. As mentioned in the Introduction,3 we provide a framework for addressing the critical next steps in designing trials to prevent PD by addressing the following questions: Who (should be enrolled)? What (to test)? and How (to measure prevention)? complemented ultimately by When during the disease (should we start these trials)?
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
