Study Rationale/Hypothesis:
The goal of this study is to determine the extent to which inflammatory factors in biofluids (cerebrospinal fluid, plasma and serum) vary throughout the course of a given day in healthy control individuals versus individuals with Parkinson’s disease. This information will tell us the time of day that inflammation should be measured in order to identify the subset of PD patients with underlying peripheral and central inflammation that might benefit from anti-inflammatory regimens to slow down progression of disease symptoms.
Study Design:
We will measure the levels of inflammatory factors in PD patients and healthy controls secreted into blood (plasma and CSF) and brain spinal fluid throughout a 24-hour period. We will examine the extent to which the levels of specific inflammatory factors vary or stay fixed throughout the day and the extent to which blood inflammation correlates with inflammation within the brain.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Information on whether the levels of specific inflammatory factors in spinal fluid or blood of healthy controls and patients with PD vary throughout a 24-hour period or with disease is lacking. Such information is needed to support the use of inflammatory factors in biofluids as valid biomarkers that can help identify PD patients with underlying inflammation for enrollment into and monitoring during clinical trials aimed at treating the underlying neuroinflammation as the driver of their disease progression.
Next Steps for Development:
Our group has been working with a novel anti-inflammatory drug, XPro1595, which has been extremely effective at blocking the loss of dopamine neurons in pre-clinical models where inflammation is promoting neurodegeneration. As a next step toward the clinic, we have devised a biomarker-directed strategy to treat PD patients with XPro1595 who are likely to benefit the most from reducing inflammation. Because XPro1595 is an anti-inflammatory drug and not a ‘PD drug’ per se, only PD patients with elevated inflammation will be eligible for enrollment into a clinical trial. For this to be successful, we need to accurately identify patients with elevated inflammation.
Progress Report
We have measured the levels of inflammatory factors in PD patients and healthy controls secreted into blood (plasma or serum) and brain spinal fluid throughout a 24-hour period. We are in the process of identifying the subset(s) of factors that fluctuate and those that stay fixed throughout a 24-hour period and the extent to which blood inflammation correlates with inflammation within the brain. Data analysis is still in progress and once completed will enable us to power a larger study that will provide much needed information on what percentage of PD subjects display central and/or peripheral inflammation relative to a matched healthy control population.