Study Rationale:
The cells residing in the brain are physically separated from the blood stream by the blood-brain barrier, a specialized grouping of cells that reduces transfer from the blood stream to the brain. This separation is essential to prevent blood-born toxins (including the Parkinson’s disease-related protein alpha-synuclein) from reaching neurons. However, the blood-brain barrier does not function optimally in patients with Parkinson’s disease, which may make disease worse by increasing the number of factors that reach these sensitive cells of the brain.
Hypothesis:
We propose that cells and proteins in the blood stream contribute to the decreased ability of the blood-brain barrier to block entrance of toxins into the brain and that this opening of the barrier contributes to the death of cells in the brain.
Study Design:
To carry out this project, we will use human cells to produce a 3D state-of-the-art model which replicates the cells and functions of the naturally occurring blood-brain barrier. The human cells will be collected from control volunteers and patients with a genetic form of Parkinson’s disease. The “peripheral circulation” side of the barrier will then be exposed to toxic forms of alpha-synuclein or to immune cells. We will measure whether these treatments allow factors to leak across the barrier and whether this increased opening decreases the health of brain cells, such as neurons.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This research study will increase our understanding of the role of the blood-brain barrier in the progression of Parkinson’s disease. Therapies aimed at preventing barrier dysfunction or restoring a healthy barrier may provide innovative new avenues to treat Parkinson’s disease.
Next Steps for Development:
The expected outcomes of the study are to propose peripheral alpha-synuclein and immune cells as drug targets, and these findings could be translated to clinical applications in the form of new therapeutic strategies.