Combination Therapy for Parkinson's Disease

There are no medications that can reverse or even slow down Parkinson’s Disease (PD) progression and the existing medications can only help motor symptoms while the disease advances. Many previously studied medications showed good results in preserving dopaminergic neurons in preclinical studies but failed to show any neuroprotection in many long, expensive clinical trials. The reasons for this include the diversity of the simultaneously occurring processes leading to neurodegeneration which cannot be addressed with just one medication. Various combinations of potentially neuroprotective medications targeting different disease mechanisms simultaneously may however show improved synergistic efficacy in slowing down Parkinson’s Disease progression.

In order to simultaneously target multiple processes that comprise the neurodegenerative cascade in Parkinson’s Disease (PD) which cannot be addressed with just one medication, we plan to screen 31 different combinations of seven preselected medications chosen for different mechanisms of their action against neurodegeneration to evaluate for additive or synergistic neuroprotective effects on a human dopaminergic neuron cell line from PD patients to select the most effective drug combination.

This combination approach can produce additive or synergistic effect needed to exhibit long awaited clinical efficacy in human trials and eventually help every single patient suffering from this devastating disease. This project, therefore, can lead to clinical development of the first treatment for Parkinson’s Disease which can slow down or reverse its progression.

I intend to test seven promising existing drugs in various combinations using stem cells models of PD to evaluate their effects on disease processes seen in PD. These seven drugs were chosen for their different mechanisms of action targeting various processes leading to neurodegeneration. All of these drugs to be tested are FDA-approved already for different indications but have never been studied in combinations in PD models. I will select one best drug combination of up to 3 drugs for further confirmation in mouse model and subsequent clinical development.