Grant: Project Grant

Multiple sclerosis (MS) is an inflammatory disease of the brain leading to paralysis, that mostly affects young adults. The majority of patients will present with a relapsing-remitting (RRMS) form of the disease in which the occurrence of symptoms (relapses) is followed by periods of partial or complete recovery (remission). In primary progressive MS (10-15%), which affects mainly men, there is a steady worsening of neurological function without intermittent recovery. Affecting more than 100, 000 Canadians, women 2-3 times more often than men, research into the exact cause and disease mechanism of MS is essential to find an effective treatment. Current treatments can temper, but not cure RRMS and no therapy is available to treat the progressive disease. The current and common mouse models for MS lack some essential disease features i.e. gender differences, spontaneous disease development, progressive disease phase and involvement of various inflammatory cells, making them inadequate to study this disease in vivo. Our goal is therefore to use a new mouse model, named the TCR1640 model, that thoroughly reflects the clinical features of MS to fully elucidate the exact disease mechanisms, that are so distinctive for MS, and to find novel specific therapeutic targets for every disease phase. We will first investigate the relationship between gender and disease development. Next, we will elucidate how different disease phases occur (relapse and progressive) and resolve (remission) from an immunological and neurological point of view. Finally, we will use this mouse model to test new therapeutic strategies for all types of MS. After this, we can look forward to implement these in MS patients. Therefore, using a mouse model that clinically and immunologically reflects human MS disease is essential to shed light on disease development, gender differences and on the untreatable progressive disease phase to find an effective treatment for all disease courses.