Grant: Project Grant

Multiple sclerosis (MS) is the most common disease of the central nervous system (= CNS; consists of the brain and the spinal cord and controls most function of the body and mind) affecting young adults. Canada has one of the highest MS incidences worldwide and people with MS are left without a treatment that cures them. Thus, there is an urgent need for novel therapeutic strategies. MS is caused by immune cells (the 'police' of the body, protecting against infections) recognizing the body's own molecules as foreign, resulting in inflammation and destruction of brain tissue. A promising therapeutic strategy is to stop these harmful immune cells from entering the CNS tissue. Here, I propose mannose receptor C type 2 (MRC2) as a novel target, which my lab has found to be located on the surface of harmful immune cells. MRC2 is known to degrade a component of the blood-brain barrier (the protecting layer separating the brain from immune cells in the blood) called collagen IV. Thus, leading to breakdown of the barrier and thereby potentially enabling harmful immune cells to enter the CNS tissue in MS. The goals of our research are (1) to study the presence of MRC2 on various harmful immune cells and its binding partner collagen IV at the blood-brain barrier; (2) to analyze whether MRC2 is associated with disease activity in people with MS, (3) investigate which stage(s) of immune cell migration MRC2 is critical for; and (4) study whether MRC2 blockade prevents harmful immune cells from crossing the blood-brain barrier, thereby preventing disease activity and progression in various animal models of MS. Our research will allow understanding of how harmful immune cells enter the CNS tissue and thereby enable development of novel therapeutic strategies to treat MS.