Measuring Altered White Blood Cell Functionality as a Biomarker of Parkinson’s Disease

Study Rationale:
White blood cells from people with Parkinson’s disease (PD) patients appear to differ from those of control individuals in that there are differences in the set of genes that are turned on in PD lymphocytes (small white blood cells) compared to controls. In our preliminary study of a subpopulation of white blood cells from PD patients, we found unexpected and dramatically altered functionality compared to control cells. This altered functionality is evidenced by a range of biochemical differences.

Hypothesis:
We hypothesize that the cellular functionality of a subpopulation of white blood cells is dramatically altered in Parkinson’s disease and will enable the identification of a suite of suitable biomarkers of the presence, duration and severity of PD.

Study Design:
Blood samples from age-matched groups of PD patients and control individuals (60 in total) will be split into two portions, one for immediate testing of fresh white blood cells and one for generation of immortalized white blood cell lines. White blood cell subpopulations will be assessed for functionality including various measures of cellular health. The results will be compared between PD and control groups and correlated with the age of the individual, time since diagnosis and a variety of clinical measures of PD severity.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This project may identify reliable, sensitive blood biomarkers that can provide objective quantitative measures for the presence, severity and progression of disease and may also explain some aspects of the underlying disease mechanisms. This will assist diagnosis, prognostic predictions of the course of the disease, and determination of the efficacy of treatments.

Next Steps for Development:
For clinical application it will be important to:

• confirm which of the tested biomarkers are unchanged during disease progression and which change with age, duration and severity of disease
• determine which of the biomarkers, if any, are affected by potential or currently used PD treatments or by other medications or treatments to which PD patients might also be exposed
• verify that the outcomes are the same regardless of patient race, ethnic and cultural background, gender, age, diet and health status
• determine how the assays are affected by transport, storage and treatment of blood under varied clinical conditions
• develop modified forms of the assays to allow reliable application to fresh lymphocytes from smaller blood samples and high-throughput implementation on a larger scale