Defining the Contribution of Neuroinflammation to Parkinson's Disease

Study Rationale:                   
Over-activation of brain immune cells, called microglia, is associated with the degeneration that occurs in Parkinson’s disease. This suggests that brain inflammation may influence the course of disease and that anti-inflammatory therapies might be useful. However, it is difficult to answer this question with the typical lab approach because the immune system of models may differ a lot from a human’s immune system. We will overcome this limitation by using a unique model with a humanized immune system to test whether specific inflammatory changes in the brain contribute to the degeneration that occurs during disease.   

Hypothesis:
We hypothesize that specific immune system changes in the brain contribute to the cell death that occurs in Parkinson’s disease.

Study Design:
We will use a specially engineered pre-clinical model with a humanized immune system that can be treated to develop a Parkinson’s disease-like condition. The behavior and brains of these models will be monitored to determine whether the course of disease relates to specific human-relevant immune changes. More importantly, we will use a clinically available anti-inflammatory drug to directly test whether the immune changes are contributing to the cell death that is occurring during disease.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
The specific changes in human immune markers we find in the brains and blood of the models will provide targets to look for in patients for tracking or possibly predicting disease. In addition, there are a range of broad and very specific immunomodulatory drugs already clinically available that could be used to inhibit the immune changes in human disease.

Next Steps for Development:
An immediate next step will be to verify that the immune changes in the model blood and brain also occur in human patients. We will then need to check whether broad anti-inflammatory drugs or targeted immunomodulatory drugs are most effective in slowing disease in the model to provide candidate drugs for human trials.