M ultiple sclerosis (MS) is a devastating pathology that mostly affects young people between the ages of 25 to 40. Among neurological diseases, MS is the most common cause of disability in young adults. Canada is known for having one of the highest rates of MS in the world (1/25,000). The disease is characterized by the progressive loss of neurological function including fatigue, vision impairment, and loss of sensory, motor, and sexual functions.
MS is classified as an organ-specific autoimmune disease and MS symptoms are associated with appearance of demyelinated plaques throughout the CNS. Interestingly, every individual has autoreactive lymphocytes, but only a small subset develops MS; this suggests that a certain conditioning of CNS is necessary for the development of the disease. The goal of my laboratory is to discover novel molecular pathways that regulate susceptibility of CNS to MS. To date, four different subtypes of plaque formation have been identified. Regardless of the type of MS and type of the plaque formation, inflammation associated with activated astroglia and microglia is one of the central components of the pathophysiology of the disease. For example, a recent study found that mutation in 29 genes, most of which regulate immune response, increases the risk of MS. For this reason, regulation of the inflammation became the key target for therapeutic strategies to treat MS. T cell activation, TLR, NFkB, and, a most recently discovered family of proteins, Nlrs have been identified as main candidates for therapeutic intervention. Upon pathogen recognition, Nlrs can activate multiple pro-inflammatory molecular pathways including formation of the inflammasome, NFkB and MAP kinase pathways. Majority of the therapies are designed to suppress immune responses globally.
As part of our research into the mechanisms of development and progression of Multiple Sclerosis, we are studying ways that augment existing feedback mechanisms to limit inflammatory response.