Funded Studies
Study Rationale: Recent studies suggest that the barrier that separates the brain from the rest of the body, including the blood, might become dysfunctional over the course of Parkinson’s disease (PD). How this barrier becomes compromised is unknown. However, its breach could allow brain cells to come in contact with detrimental blood-borne factors, such as pro-inflammatory signals, that accelerate the loss of neurons and the development or progression of the disease.
Hypothesis: We hypothesize that peripheral immune cells secrete molecules that can compromise the blood-brain barrier and thereby induce neuronal loss.
Study Design: We established a tissue-engineering system using a microfluidic model of the blood-brain barrier to study the interactions between peripheral immune cells, the brain vasculature and neurons. Using this model, we will identify receptors located at the interface of the brain vasculature that may be involved in relaying toxic signals from the blood to the brain. We will also identify lipids and lipid particles that may contribute to the neurotoxic properties of peripheral immune cells.
Impact on Diagnosis/Treatment of Parkinson’s disease: Identifying the peripheral receptors and molecules that contribute to PD onset and progression could provide attractive targets for novel therapeutics that would not need to enter the brain to prevent neuron loss. An inability to reach the brain is a significant source of drug failure in clinical trials.
Next Steps for Development: Discovery of peripheral immune targets will facilitate the design of immune-modulatory drugs for people with PD. The identification of vascular receptors capable of relaying detrimental signals to the brain would provide new strategies for the design of small molecules therapeutics.