Project 462072

Multiple sclerosis (MS) is the most common cause of neurological disability, other than trauma, in young adults. Approximately 100,000 Canadians, and over two million people worldwide have MS. Canada already has one of the highest rates of MS in the world, and by 2031 it is predicted to increase by 33%. The annual cost of MS to the Canadian Health Care system is expected to reach $2 billion, and does not include roughly $170M out-of-pocket expenses for patients in associated health care costs. MS symptoms vary widely and may affect sight, hearing, memory, balance, and movement. This all leads to a decreased ability to work, care for a family, and a poor quality of life. To date, there is no cure or prevention for MS, and over time, MS enters a highly disabling progressive phase. Although treatments to effectively manage the clinical symptoms of MS are available, they come with serious, and even life-threatening consequences. To develop more effective treatments for MS, we require a better understanding of the biological processes of susceptibility and progression, as well as animal models that emulate human disease. To address these limitations, we have developed the first mouse model of MS based on a human mutation that causes primary progressive MS in families. Preliminary analysis of this model has already revealed parallels with human disease; thus we hypothesize that the comprehensive molecular and biological characterization of this model will identify the underlying biological mechanisms responsible for the onset of MS in patients, and provide the tools for the development and evaluation of more effective therapeutics for progressive disease. Ultimately, our objective is to use our new model of human MS to gain a better understanding of the biological processes of disease, and to develop treatments that provide neuroprotective benefit, alleviate clinical symptoms and lessen the burden of MS in patients and society.