Dr. Abid Oueslati
Laval University
Pedaling for Parkinson’s New Investigator Award
New Investigator Award
$90,000 over two years

Creation of a cell and animal model of the propagation of α-synuclein and identification of authentic prion forms of this protein

Abid Oueslati’s fascination with the brain began as part of his initial experiences with scientific research in France. Later, while pursuing post-doctoral studies in Switzerland, he began to tackle Parkinson’s disease as a bio-molecular puzzle whose solution could improve the lives of patients around the world.

One molecule in particular captured his imagination: the intricate protein known as α-synuclein, which can spread through the brains of Parkinson’s disease patients as the ailment develops. For Oueslati, who is now an assistant professor in molecular medicine at Laval University, this behaviour closely resembles that of another problematic protein, the notorious prion.

Scientists first identified prions about 20 years ago in the search for the causes of mysterious plaques that formed in the brain and broke down its network of connections, leaving an affected person or animal increasingly disabled. The culprit turned out to be these strange proteins whose molecular structures are folded in awkward patterns and move between brain cells to disrupt healthy tissue. Oueslati has seen a similar pattern to the way α-synuclein affects the brain.

“It makes plain the progress of the disease,” he says. “It’s opening up a new area of research into Parkinson’s disease because it shows a new mechanism. It also offers new opportunities for new therapies — stopping or at least reducing the disease progress.”

Parkinson Canada is supporting Oueslati’s work, which he regards as the initial building block that will help him establish an ongoing research program in this field.

“This is a tremendous help to jump-start this project,” he explains. “We’ll be able to collect data and publish the first conception of what we want to do.”

Among the most significant developments he anticipates will be a far more effective laboratory procedure for studying Parkinson’s disease in mice. Researchers currently try to mimic the condition by adding excessive amounts of α-synuclein into the brains of these animals, but the technique yields haphazard results. By applying a model of prion-like propagation, however, Oueslati has been able to use viruses to deliver the protein into the brain in a way that more closely resembles the advance of Parkinson’s.

“The problem today is one of reproducibility,” he explains. “Our purpose is to develop an accurate, simple, and controllable model.”

He is also taking stem cell samples from Parkinson’s patients and growing them in culture to learn more about genetic features that might be responsible for the condition in the first place.

“This is a new field,” Oueslati notes, “which could show the vulnerability of these cells to some kind of external event that leads to Parkinson’s.”