Objective/Rationale:
A normal function of inflammation is to recruit phagocytic white blood cells (think PACMAN) to clear away the damaged cells. We postulate that debris laden PACMEN re-enter the blood stream in sufficient numbers to measure brain substances inside these PACMAN cells. Looking for substances that are only found in the nerves destroyed by Parkinson’s disease (PD) in these white blood cells may enable early detection of PD with a blood test.
Project Description:
The nerves that are affected by PD are in a brain region called the substantia nigra. We will use ultra thin slices of normal substantia nigra to test whether a known melanin binding substance can bind to neuromelanin in the nerves of the substantia nigra. The substance will be tagged with a dye which we will look of under the microscope after it has been layered on the substantia nigra and then washed off. If we find that the substance does bind to neuromelanin we will then grind up cells containing neuromelanin to develop a biochemical binding test for neuromelanin using pigmented epithelial cells from the retina of the eye (which is actually a part of the brain). Once we have created this biochemical test on cells and show that it works, we will do experiments to show that normal white blood cells don’t have any neuromelanin in them. Now we can do a pilot experiment with white blood cells from newly diagnosed PD subjects to show whether or not we can detect neuromelanin in them.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Early detection of PD means early treatment that offers the prospect of controlling the disease before symptoms arise and thus preserving quality of life. Early detection will also help therapy development of neuroprotective drugs for PD.
Anticipated Outcome:
We expect to show that a small molecule that binds to melanin can detect neuromelanin in nerves that are the target of PD and that we can use this substance to detect neuromelanin in white blood cells so that we can develop a blood test for neurodegeneration that can detect PD early. This will pave the way for larger studies to validate the blood test.
Final Outcome
We have succeeded in developing an assay for neuromelanin and showed that it can detect melanin within cells. We attempted to use this method to detect white blood cells that contain neuromelanin as a consequence of clearing away of dead cells in the brain. We have shown that neuromelanin can be detected in cells in the blood of eight of 10 established PD subjects. Further studies in subjects at high risk for developing PD will reveal whether this measurement will detect PD at an early stage when dopaminergic neurons could be saved and development of PD prevented.
March 2014