Targeting T Cell Metabolism to Reduce Neuroinflammation in Multiple Sclerosis
Year Awarded: 2019
Term: 3 years
Funding Amount: $386,350
Affiliation(s): Centre de Recherche du CHUM
Researcher(s): Dr. Catherine Larochelle
Summary: Western diet, obesity and related comordities are risk factors for MS onset and progression. Scientific evidence shows that restricting intake of methionine, an essential amino acid found in high-levels in meat-based diets, is associated with a prolonged lifespan (anti-aging), slower cancer progression, lower cardiovascular comorbidities, and reduced inflammation in obese mice and in an inflammatory bowel disease model. In contrast, high methionine intake is associated with cardiovascular and cognitive problems. This research explores the impact of restricting dietary methionine and inhibition of the methionine metabolic cycle on MS using animal models.
Project Description: Recent research studies found that red meat consumption is higher in MS than in control populations, and that higher intake from saturated fat increases the risk of relapse in pediatric MS. Moreover, the prevalence of cardiovascular comorbidities is rising in the MS population and correlates with worse disability. Diet, obesity and related comorbidities can influence the activation of the immune system. T cells, a type of immune cells, are believed to orchestrate an 'attack' on the immune system in the brain and spinal cord in MS. These T cells use available nutrients to proliferate and produce pro-inflammatory factors that lead to injury of the nervous system. Research from this group, led by Dr. Catherine Larochelle, identified that lower methionine intake affects differentiation of T cells (called Th17) and onset of MS-like disease in mice, establishing a novel link between methionine metabolism and neuroinflammation. The goal of this project is to characterize the potential of novel interventions targeting the methionine cycle in order to manipulate T cells and reduce neuroinflammation in MS in the animal model. Manipulation of methionine metabolism represents a new therapeutic avenue in MS.
Potential Impact: This project will lay the foundation for dietary intervention studies in people with MS, and for testing pharmacological inhibitors of methionine metabolism. These inhibitors are currently in clinical trial for cancer. Dietary interventions could represent a cost-effective and low risk measure to prevent and control MS. Metabolic pathways affecting activation of T cells could represent entirely novel therapeutic targets.
Project Status: In progress
Latest MS Research News: