T Cell-mediated Autoimmune Responses in Parkinson's Disease

Research Grant, 2017

Study Rationale
The protein alpha-synuclein, which is misprocessed in nearly every case of Parkinson's disease (PD), forms the Lewy bodies seen in PD patient brain. In our recent MJFF-funded study, our labs identified an autoimmune feature in PD, specifically a response by the immune cells known as T cells to alpha-synuclein in people with PD. It is possible that an autoimmune response leads to the death of neurons in PD. Here we intend to characterize these responses and expand the research to investigate the self-regulatory features of the immune system.

Hypothesis
We hypothesize that several processes that normally keep alpha-synuclein and other PD proteins handled efficiently, are disturbed in PD, which may lead to a neurodegenerative autoimmune response.

Study Design
Working with outstanding PD clinics at Rush University Medical Center (Dr. Jennifer Goldman) and UC San Diego (Dr. Irene Litvan), we will analyze people with PD and age-matched control volunteers for the responses of immune cells to a range of potential misprocessing steps.

Impact on Diagnosis/Treatment of Parkinson's Disease
This work could lead to blood tests that would identify PD in early stages, so that treatments that might slow progression could begin earlier, and could provide a measure of efficacy for treatments that might treat the autoimmune features.

Next Steps for Development
If this work is successful, we may be able to design specific new therapies that directly target the autoimmune responses.