Project Overview

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and the fastest growing neurodegenerative disorder worldwide. However, despite extensive investigation, most clinical trials failed to translate promising findings into drugs for people living with the disease. As of today, there is no therapy that can stop or slow PD progression, and drug discovery efforts remain critical to ameliorate the lives of more than 100,000 Canadians. Some of the reasons for these challenges are the lack of faithful animal models that spontaneously develop features of the disease (rodents do not naturally develop PD) and in vitro models that recapitulate the complexity of living tissues. In particular, the difficulty to predict if a drug candidate can cross the restrictive blood brain barrier (BBB) in humans is a major drawback of current drug discovery platforms. We therefore hypothesize that an improved in vitro platform that reproduces tissue-level organization using human cells would support drug discovery efforts. Our objective is to develop an innovative brain-on-chip platform that reproduces complex brain-body interactions at the cellular and molecular levels.

The proposal is organized into two research Aims to (1) establish a mini-brain irrigated by a dense network of blood vessels and (2) characterize how the blood composition of people with PD affects the cells residing in the brain tissue. To do so, we will build on a microfluidic model of the human BBB that we previously established using human induced pluripotent stem cells. Then, we will use novel molecular tools to track the birth of new cells in the midi-brain irrigated with plasma from healthy donors of people with PD. Overall, successful completion of this project will provide the scientific community with an advanced model that can be scaled-up for preclinical drug discovery screening while allowing the investigation of disease mechanisms.

Principal Investigator

Aurélie De Rus Jacquet , Université Laval