A Roadmap for Future Parkinson's Pharmacogenomics in Asia

Parkinson’s disease (PD) remains one of the most debilitating neurodegenerative diseases, with increasing prevalence worldwide. Due to the demographic transition ongoing in many countries, life expectancy is increasing, whilst chronic and degenerative conditions such as Parkinson’s also rise with aging (Dorsey et al., 2018). The disease is typically seen in persons 60 years of age or older who are already more likely to experience additional burden due to limited physical, cognitive, and emotional capacity in their day-to-day lives. However, it is notable that earlier onset of the disease have been identified in a small subset of patients (Post et al., 2020). When left untreated, PD can exert a negative long-term impact on the quality of life of both the patient and the caregiver (Asimakopoulos et al., 2008). Although the exact pathogenesis of the disease remains elusive, it has been suggested that it develops as a results of dopaminergic neuron degeneration in the substansia nigra (Schulz- Schaeffer, 2010). Pharmacotherapy still relies on traditional agents such as levodopa, despite the emergence of novel agents and elective surgical interventions such as deep brain stimulation that has been shown to provide long-term improvement of motor function (Limousin and Foltynie, 2019). Levodopa remains the most clinically-effective and cost-effective Parkinon’s disease treatment, which can provide an adequate success rate in the majority of cases upon administration that considers the most optimal bioavailability and efficacy. However, a subset of patients may experience the occurrence of motor levodopa-induced complications, including levodopa-induced dyskinesia or motor fluctuations, rendering the levodopa treatment ineffective (Soraya et al., 2022). Although Asia had the largest number of PD incidence in 2019, a lower prevalence of PD has been documented in Japan and Singapore, despite having a relatively high proportion of aged individuals. Moreover, it is notable that sex-related differences have been reported in PD prevalence, clinical phenotypes, and prognosis. Hence, these findings pinpoint that genetic and environmental risk factors may play an important role to the differences observed in the region.