Pharmacogenomics-a New Frontier for Individualized Treatment of Parkinson's Disease

Curr Neuropharmacol. 2023;21(3):536-546. doi: 10.2174/1570159X21666221229154830.

Abstract

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects.

Objective: This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs.

Methods: In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions.

Results: This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted.

Conclusion: Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.

Keywords: Parkinson’s disease; drug response; genetic phenotypes; genetic polymorphism; individualized medicine; pharmacogenomics.

Publication types

  • Review

MeSH terms

  • Antiparkinson Agents / therapeutic use
  • Drug-Related Side Effects and Adverse Reactions* / drug therapy
  • Humans
  • Levodopa / therapeutic use
  • Neurodegenerative Diseases* / drug therapy
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / genetics
  • Pharmacogenetics / methods
  • Prospective Studies

Substances

  • Antiparkinson Agents
  • Levodopa