Grant: Project Grant

Western diet and obesity are risk factors for multiple sclerosis (MS), an inflammatory neurological disorder affecting 1 in 500 Canadians. Diet and obesity influence the activation of the immune system, a key player in MS. Immune cells are indeed considered to orchestrate an aberrant 'attack' of the immune system against the brain and spinal cord in MS. Immune cells use available nutrients to proliferate and to produce proinflammatory factors that lead to injury of the brain and spinal cord. By limiting the presence of the essential amino acid methionine in the culture medium of immune cells, we were able to decrease their activation and to limit their production of pro-inflammatory factors. Importantly, restriction of methionine in the diet of the mouse model of MS resulted in a significant delay of onset of MS-like symptoms. Based on these results, we propose to investigate the role that methionine metabolism has on the activation of the immune system and its capacity to infiltrate the brain and spinal cord in animal models of MS. Since methionine metabolism can differ between men and women, and as MS frequency and evolution are influenced by biological sex, we will specifically assess the impact of dietary methionine intake on the risk to develop MS-like symptoms in males versus in females in an active and a spontaneous mouse model of MS, as the latter mimics the course of MS in humans. We will use these pre-clinical models to identify the mechanisms by which manipulating methionine influences the activation and function of the immune cells, including through regulation of the expression of genes for immune-related factors. We will also investigate if methionine metabolism is different in MS patients according to sex and versus healthy controls. This proposal will assess whether we can use specific dietary and pharmacological interventions modulating immune cell methionine metabolism as a therapeutic intervention to improve MS in women and men.