Grant: Project Grant

Canada has one of the highest rates of multiple sclerosis (MS) in the world, with 1 in every 250 Canadians affected. This translates into a considerable societal and economic burden ($1.6M per patient). At present, it is not possible to reverse the neuron damage in MS. Therefore, the best chance of curing this disease is to prevent it from starting in the first place. Thus understanding the risk factors for development of MS and the biology of how these risk factors initiate the disease process is an important area of research. Three times more women than men develop MS, and we still do not understand why this is the case. In addition, if men get this disease, they tend to exhibit more rapid progression. Our goal is to better understand the fundamental biological differences that account for the greater susceptibility of females to develop MS and for men to develop more rapid progression. Here, through studies in mice and in human MS patients, we are trying to better understand the nuts and bolts of why the immune response may be more vigorous in females and can lead to the initiation of autoimmunity. We are pursuing the novel hypothesis that the reason why females are more prone to develop MS is because they have more T cells that can recognize the myelin sheath. We have thus far found evidence of this in the peripheral blood of human patients and in a mouse model of this disease. Further studies are planned in mice to get to the underlying mechanisms for this sex difference in T cell numbers. We are also going to characterize the immune cells in men and women with MS in order to gain new insights into how the disease may be different between the sexes. Understanding this biology will improve our understanding of how MS gets started and may lead to new ways of preventing or treating this disease. .