Grant: Project Grant

Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS) with high prevalence in young adults. The clinical symptoms of MS are the result of self-targeting immune cells migrating across the brain and spinal cord blood vessels into the CNS, where they cause destruction to the myelin insulation surrounding the nerve cells (a process that does not occur in healthy individuals). Cell adhesion molecules (CAMs) on immune cells are essential mediators of immune cell migration across blood vessels. While current MS therapies are able to decrease the number of relapses, none are able to completely prevent or halt disease progression, and many carry severe risks resulting from immune suppression. Thus, identifying novel, specific targets to prevent harmful immune cells from entering the CNS is a major therapeutic goal to prevent MS disease activity and progression. My lab has identified a novel CAM, integrin alpha8 (alpha8), on a harmful subset of immune cells in MS. The binding partner of alpha8, nephronectin, is found on the CNS blood vessels, suggesting that it might facilitate the entry of alpha8-bearing immune cells into the brain and spinal cord. The goals of our research are (1) to study the presence of alpha8 on various harmful immune cells and its binding partner nephronectin on the CNS blood vessels; (2) investigate which stage(s) of immune cell migration alpha8 is critical for; (3) study whether alpha8 blockade prevents the pathogenic immune cells from crossing the CNS blood vessels, thereby preventing disease activity and progression in various animal models of MS and (4) determine whether alpha8 is an effective biomarker of disease activity and response to treatment in MS. A better understanding of the mechanisms by which harmful immune cells enter the CNS in MS is critical for the development of new therapies that prevent CNS damage and therefore ward off or inhibit disease progression.