Computational Modeling of Multi-drug Therapy in Parkinson's Disease

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder in the world after Alzheimer’s. The hallmark symptoms of PD are tremor and rigidity, which are caused by the death of dopaminergic neurons in the basal ganglia. These symptoms are often treated by levodopa (L-DOPA), MAO-B inhibitors, and other pharmaceuticals with the goal of increasing dopamine in the brain. To better understand the underlying mechanics of L-DOPA and its clinical effects on patients, various computational models have been developed. One model, by Véronneau-Veilleux et. al (Chaos 30, 093146, 2020), integrates L-DOPA pharmacokinetics, dopamine dynamics, and a neurocomputational model of the basal ganglia to predict the impact of L-DOPA regimens on a patient's motor function. In this study, we extended the model to investigate the interactions of L-DOPA with other pro-dopamine drugs and dosing regimens to provide a framework for improving treatment strategies.