Are we ready for PD prevention studies?

Abstract

Over the last two decades a substantial progress has been made in understanding of Parkinson's disease biology and natural history. Most relevantly, the syndrome of premotor (prodromal) manifestations (hyposmia, REM behavior disorder, sleep, autonomic dysfunction among the others) and genetic risk factors have been well defined. On the other hand, not a single disease modifying trial had a positive effect on disease progression despite multiple trials. One of the potential explanations of the recent failures is late timing of intervention as newly diagnosed PD is already associated with significant loss of dopaminergic and other neurons. Constellation of recent failures and better understanding of the scope and natural course of prodromal phase of the disease pave the way to disease prevention studies. Such studies will target prodromal population and test efficacy of intervention to prevent pphenoconversion to clinically defined alpha- synucleinopathy. In order to plan such studies, we need to define the population (WHO), intervention (WHAT) and finally how to measure success (HOW). While a number of observational studies have provided substantial data on the risk of pheconversion in prodromal cohorts to clinically defined a-synucleinopathy, still the challenges remain. An essential aspect of readiness for disease prevention studies is a number of ethical and feasibility considerations of testing interventions in prodromal at-risk participants who do not have disability or clinically defined disease. This presentation will review the state of the field in regard to readiness for PD prevention studies and outline future directions.