Grant: Project Grant

Multiple sclerosis (MS) is an incurable, severely debilitating disease with suboptimal therapy and no cure. Canada has the highest incidence of MS in the world with 291 cases per 100,000 people. MS is most commonly diagnosed in young adults and patients suffer progressive and irreversible damage to the brain. The root causes and risk factors for MS are still unknown. As such, current therapies are limited to treating symptoms, rather than the root cause. Other incurable diseases that lead to progressive loss of quality of life, and death, include the occupational respiratory diseases; which are caused by breathing in toxic materials such as asbestos and silica. These diseases commonly affect our firefighters, miners and military personnel. MS and occupational respiratory diseases are caused by chronic inflammation of the brain and lung respectively. Although the brain and lung have very different functions in the body, they share some common features during inflammation. One common feature is that the inflammatory protein IL-1 is made by cells locally and leads to excessive inflammation and tissue damage. It is well known that if we limit IL-1, we can protect from MS and occupational respiratory diseases; but we don't fully understand how and why IL-1 is made. We have exciting new evidence to suggest that a recently found digestive protein in immune cells triggers the release of IL-1 in both the brain and lung. Mice that don't have this protein are protected from experimental models of MS and respiratory disease caused by silica. Interestingly, this protein was recently identified by other scientists as being a possible risk factor for MS. Our research will determine how this protein brings about IL-1 release and inflammation in the brain and lung. This will allow scientists and doctors to better understand how chronic inflammation develops and potentially formulate new strategies to treat diseases such as MS and occupational respiratory disease.