Un système de culture microfabriqué pour étudier la régulation de la myéline dans le système nerveux central et identifier les thérapies de remyélinisation

 

Daryan Chitsaz

Institut et hôpital neurologiques de Montréal

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Formation de doctorat

Concours 2019-2020

Partenaire:

Société canadienne de la sclérose en plaques

In the disease multiple sclerosis (MS), a substance that coats the nerves in your brain known as "myelin" is destroyed by your own immune system, leading to severe neurological dysfunction and neuronal death. A major problem in MS is the lack of myelin regeneration: due to a "plaque" of toxic factors released during these immune attacks, new myelin-producing cells are unable to access the damaged site and repair it. We hope to find new drugs to overcome this repulsive MS plaque by systematically testing compounds on myelin-producing cells grown in a cutting-edge experimental system we have developed. We can grow these cells in a microengineered culture system which reproduces their three-dimensional environment in the brain, visualize them automatically with sophisticated microscopes, and rapidly analyze them with an artificial intelligence program. To study how myelin-producing cells respond to MS plaques, we will stamp a plaque-associated protein on the culture devices and characterize how it repels them.

We will then screen a battery of potential drugs to find compounds which allow these cells to ignore the plaque, and produce new myelin despite it. Ultimately, we will test any promising compounds on human myelin-producing cells cultured with actual plaque harvested from autopsies of MS patients, allowing us to more accurately gauge whether they could be clinically useful. Thus, we will identify new mechanisms and potential therapeutics to promote remyelination, create and disseminate powerful new tools to accelerate research by other MS labs, and improve our understanding of the disease's mechanism with human cells.