Grant: Project Grant

Despite the introduction of several immune-modulating therapies in relapsing-remitting Multiple Sclerosis, treatment for many patients remains inadequate. There are also no treatments for patients with the progressive forms of Multiple Sclerosis. Thus, it is important to identify hitherto unrecognized factors that might promote inflammation and neurodegeneration in Multiple Sclerosis, and which are not currently targeted by medications. The Yong Laboratory has identified alterations in the extracellular matrix in the brain of patients with Multiple Sclerosis and in animals afflicted with a Multiple Sclerosis-like pathology. Specifically, there is the accumulation of a group of chemicals named chondroitin sulfate proteoglycans (CSPG) in the brain matrix particularly in regions called perivascular cuffs, which are sites where immune cells gather before entering the brain. In preliminary experiments, CSPGs promote immune cell activity in tissue culture studies. Thus, the current research proposal seeks to define the roles of CSPGs in the disease process of Multiple Sclerosis. Moreover, the projects seek to invent and test new medications to reduce the production of CSPGs in lesions of Multiple Sclerosis. In summary, the goal of this proposal is to develop a new treatment for patients with Multiple Sclerosis through the identification of a novel factor in the pathogenesis of inflammation and neurodegeneration, the CSPGs.