From diagnosis to function: the pathophysiological significance of intra-thecal antibody responses to lipids in multiple sclerosis

Multiple sclerosis (MS) is the most common cause of chronic disability among young adults in the UK and affects over 1 in 500 people in Scotland. However, despite recent advances, the efficacy of current treatments remains limited by factors including large numbers of non-responders and severe adverse effects. Developing prognostic tools to classify patients for treatment, identify those at risk of developing potentially fatal adverse effects and in general, help patients make informed lifestyle changes are now a matter of urgency.
Building on previous studies demonstrating MS is associated with lipid-specific autoantibody-responses, we have identified a previously unknown mechanism by which these antibodies act to exacerbate disease activity in Central Nervous System (CNS) inflammation, whilst at the same time reducing their risk of developing a commonly fatal opportunistic viral infection, progressive multifocal leukoencephalopathy (PML).
This project will determine which lipid-specificities are responsible for these different biological responses, identify the signalling pathways involved and validate their clinical significance. These studies will lead to the development of new prognostic/diagnostic tools that will improve the clinical management of multiple sclerosis, as well as providing new insights into factors contributing to disease development.