Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy

Understanding the pathophysiology and genetic background of Parkinson's disease (PD) increases the likelihood of developing effective disease-modifying therapeutic strategies. In particular, the discovery of genetic variants causing or increasing the risk for PD has contributed to refining the clinical, biological, and molecular classification of the disease and has offered new insights into sporadic forms. It is even more evident that specific genetic mutations can show different responses to pharmacological and device-aided therapies. To date, several agents acting on multiple PD-causing pathogenic pathways have been tested as disease-modifying strategies, with disappointing results. This may be caused by the recruitment of PD populations whose underlying molecular pathophysiology is heterogeneous. We believe that an effective model of personalized medicine must be prioritized in the near future. Here, we review the current therapeutic options under clinical and preclinical development for PD and discuss the key pending questions and challenges to face for successful clinical trials. Furthermore, we provide some insights into the role of genetics in guiding the decision-making process on symptomatic and device-aided therapies for PD in daily clinical practice.

Automated summary

Understanding the pathophysiology and genetic background of Parkinson's disease is crucial for developing effective disease-modifying therapeutic strategies. The discovery of genetic variants causing or increasing the risk for PD has contributed to refining the classification of the disease and guiding the decision-making process on different therapies. However, the heterogeneity in molecular pathophysiology among PD populations may explain the disappointing results of current disease-modifying strategies. Personalized medicine should be prioritized in the future. This review discusses the current therapeutic options for PD and the challenges in successful clinical trials, as well as the role of genetics in guiding treatment decisions in daily clinical practice.