Grant: Project Grant

Multiple sclerosis (MS) is a neurological disease in which immune cells invade the brain and spinal cord leading to destruction of a fatty substance around nerve cells called myelin. Because myelin is important for the health and proper function of nerve cells (aka neurons), these nerve cells eventually die or do not work as well. As a consequence, people with MS have issues with movement, thinking and sensation. There are over 20 FDA-approved therapies that stabilize the disease for some people with relapsing-remitting MS. However, most individuals with MS still progress to a highly disabling form called progressive MS for which there are no effective medicines. Progression in MS is linked to death of neurons but we do not understand what triggers their destruction. If we can identify the triggers, we may be able to prevent or delay disability in the disease. Based on preliminary data, we postulate that a change in the composition of the gut microbiome may be one such trigger because the gut microbiota is not only different in people with MS as compared to healthy individuals, but gut microbes are known to both positively and negatively affect how the cells in the brain and spinal cord work. Further, there is some evidence that the composition of the gut microbiota is different between people with progressive disease vs those with relapsing-remitting MS. As such, we will investigate if a change in the gut microbiota contributes to the development of progressive MS. To test this idea, we will use a unique mouse model in which some animals develop a progressive MS-like disease. Intriguingly, we discovered that gut microbes are different between animals that progress versus those that do not. We thus aim to determine in this grant if identifying and administering the 'good' gut microbes and/or their secretory products (possible therapeutics) will prevent the development of progressive disease and if they do, is it because of decreased death of nerve cells.