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

Abstract

ABSTRACT Introduction Although there has been substantial progress in research and innovations in symptomatic treatments, similar success has not been achieved in disease-modifying therapy (DMT) for Parkinson’s disease (PD). Considering the enormous motor, psychosocial and financial burden associated with PD, safe and effective DMT is of paramount importance. Areas covered One of the reasons for the lack of progress in DMT for PD is poor or inappropriate design of clinical trials. In the first part of the article, the authors focus on the plausible reasons why the previous trials have failed and in the latter part, they provide their perspectives on future DMT trials. Expert opinion 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.