Parkinson's disease pharmacogenomics: new findings and perspectives

Abstract

Parkinson's disease (PD) is unique among neurodegenerative disorders because a highly effective pharmacological symptomatic treatment is available. The marked variability in drug response and in adverse profiles associated with this treatment led to the search of genetic markers associated with these features. We present a review of the literature on PD pharmacogenetics to provide a critical discussion of the current findings, new approaches, limitations and recommendations for future research. Pharmacogenetics studies in this field have assessed several outcomes and genes, with special focus on dopaminergic genes, mainly DRD2, which is the most important receptor in nigrostriatal pathway. The heterogeneity in methodological strategies employed by different studies is impressive. The question of whether PD pharmacogenetics studies will improve clinical management by causing a shift from a trial-and-error approach to a pharmacological regimen that takes into account the individual variability remains an open question. Collaborative longitudinal studies with larger sample sizes, better outcome definitions and replication studies are required.