Identifier et cibler les mécanismes immunitaires contribuant aux dysfonctions de la neuroglie dans les maladies neuroinflammatoires

 

Catherine Larochelle

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers cliniciens - Junior 1

Concours 2018-2019

Multiple Sclerosis (MS) is a chronic inflammatory disease of the brain and spinal cord, associated with debilitating neurological symptoms. Available treatments have serious shortcomings: people affected by the progressive form of MS, which are generally older, are resistant to available therapies. Drug-refractory epilepsy is another treatment-resistant chronic disease of the brain causing incapacitating symptoms. Recent studies suggest that inflammation also plays a role in epilepsy.

Pro-inflammatory immune cells can be deleterious to the cells of the brain and spinal cord. They express specific ‘cell adhesion molecules', which are molecules that they use to talk with and stick to other specific cells that express the complementary ligand. Using these sticky molecules, they are able to infiltrate the brain and spinal cord. Once there, they cause damage by calling other immune cells and secreting factors that promote inflammation, but also by directly contacting cells of the brain. These inflammatory immune cells are more frequent in the blood of people with MS than controls, and some increase upon aging. Moreover, recent studies report they are also present in the blood of patients with refractory epilepsy.

With my research program I plan to uncover molecules that are used by inflammatory immune cells to stick to cells of the brain and spinal cord and cause damage. I also aim to identify markers of aging immune cells that would predict progression of disability and resistance to treatment in MS. Finally, I will determine if specific pro-inflammatory immune cells are more frequent in the blood of people affected by drug-refractory epilepsy than controls. The immune markers identified could become treatment targets to limit the damage to the cells of the brain and spinal cord and therefore the accumulation of disability, as well as to restore good conditions for regeneration/repair in MS and in drug-refractory epilepsy.