How should future clinical trials be designed in the search for disease-modifying therapies for Parkinson's disease?

There are several potential reasons why previous trials have failed, including broad clinical and etiopathogenic heterogeneity of PD, poor definition and documentation of target engagement, lack of appropriate biomarkers and outcome measures, and short duration of follow-up. To address these deficiencies, future trials may consider- (i) a more customized approach to select the most suitable participants and therapeutic approaches, (ii) explore combination therapies that would target multiple pathogenetic mechanisms, and (iii) moving beyond targeting only motor symptoms to also assessing non-motor features of PD in well-designed longitudinal studies.