Grant: Operating Grant

Multiple sclerosis (MS) is an autoimmune disease leading to central nervous system (CNS) degeneration in approximately 2.5 million people worldwide including 55,000-75,000 Canadians. Current therapies for MS are useful in some patients but they do not prevent progression of the disease and are ineffective in many patients signifying a vital need for new therapies. My research interest is to identify endogenous protective molecules and/or mechanisms in MS that suppress autoimmunity and CNS damage in order to prevent the progression of MS. This research has tremendous potential for discovering novel strategies to treat MS. AlphaB-crystallin (alphaBC) is the most abundant gene found to be upregulated in early, acute MS plaques with localization to CNS glia. Free alphaBC is also detected in sera and cerebrospinal fluid (CSF) of all relapsing-remitting MS (RRMS) patients but only a proportion of individuals with other neurological disorders (eg. epilepsy, cancer). We found that in mice with experimental allergic encephalomyelitis (EAE), an animal model of MS, this crystallin acted as a "brake" on inflammation by attenuating the pro-inflammatory activity and CNS infiltration of leukocytes. Most significantly, recombinant human alphaBC (rhualphaBC) was therapeutic in ameliorating clinical EAE. However, the underlying mechanisms of rhualphaBC treatment, and the translation of the EAE results to MS, remain undefined. This study aims to identify the immunological mechanism(s) underlying rhualphaBC therapy in EAE, as well as test the ability of this crystallin to suppress the activity of immune cells from MS patients. I will also investigate the role of alphaBC in the physiology of oligodendrocytes, the cells primarily targeted for death in MS. This research will advance our knowledge on the role of alphaBC in MS, as well as place us one step closer to determining whether this crystallin may have therapeutic potential in MS.