Parkinson’s Disease Treatment and the Role of Genetic Polymorphisms in the Efficacy and Adverse Effects

Abstract

Parkinson’s disease (PD) is a relentlessly growing neurodegenerative disorder clinically manifested by rigidity, tremors, and dyskinesia ascribed to loss of nigrostriatal dopaminergic innervation.  Conventional therapies focus on alleviating disease symptoms as far as possible, yet lack the ability to halt the progression of the neurodegenerative process. A major historic turning point in PD therapy came through the inception of levodopa (l-dopa), however, its prolonged use is associated with complications and a decline in response. Some alternate modalities to treat PD are also available as dopamine agonists (DA), catechol-o-methyl transferase inhibitors (COMTIs), and non-dopaminergic drugs that could be used as a supportive therapy with l-dopa or alone. Nonetheless, these drugs are less effective than l-dopa in regulating motor symptoms. On the other hand, substantial inter-individual variations are observed in response to l-dopa. Although many factors can influence an individual’s response to therapy, a patient’s genetic makeup could be a starting point in creating precision medicine with greater safety and efficacy. Precision medicine that incorporates pharmacogenomics data can optimize patients’ response to PD drugs and facilitate treatment. In this review, we aim to present PD pathogenesis, challenges of current therapy, and pharmacogenetics aspects of levodopa.