Study Rationale: The cells of the brain are physically separated from the rest of the body by the blood-brain barrier, a network of blood vessels that restricts transfer of materials from the bloodstream to the brain. This separation prevents blood-borne toxins — including the alpha-synuclein protein that accumulates in Parkinson’s disease (PD) — from reaching neurons in the brain. In people with PD, the blood-brain barrier does not function optimally, which worsen the condition by increasing the amount of alpha-synuclein and other toxins that reach these sensitive cells of the brain.
Hypothesis: We propose that cells and proteins circulating in the bloodstream reduce the ability of the blood-brain barrier to block the passage of toxins into the brain and that this disruption of barrier function contributes to the neurodegeneration that occurs in PD.
Study Design: In this project, we will use human cells to produce a three-dimensional, state-of-the-art model that replicates the structure and functions of the naturally occurring blood-brain barrier. The cells will be collected from healthy volunteers and individuals with a genetic form of PD. The side of the barrier representing peripherally circulating blood will be exposed to toxic forms of alpha-synuclein or to immune cells. We will then identify the conditions that allow factors to leak across the barrier and determine whether this increased porousness impairs the health of brain cells, such as neurons.
Impact on Diagnosis/Treatment of Parkinson’s disease: This study will increase our understanding of the role of the blood-brain barrier in the progression of PD. Therapies aimed at preventing barrier dysfunction or restoring a healthy barrier may provide exciting new avenues to treat PD.
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.