Grant: Operating Grant

Scores of genes and proteins are increased in the brains of multiple sclerosis (MS) patients but the function of most of these molecules is poorly understood. These factors may contribute to development of the disease, progression of disability or attempts for repair, and understanding their roles may lead to the discovery of novel treatments for MS. Cystatin C gene is increased in the brains of people with MS as well as in mice with experimental allergic encephalomyelitis (EAE), a model of MS. The function of this protein in MS and EAE is unknown and conflicting evidence exists as to whether it could be a protective or detrimental molecule. Previous work had hailed CysC as a biomarker for MS but the results could not be replicated. On the other hand, CysC has been shown to be protective in collagen-induced arthritis (CIA). Since CIA is an autoimmune disease like MS, we hypothesized that CysC may also be a beneficial molecule in MS. To our surprise, our preliminary data suggests that CysC may in fact be a detrimental molecule in MS since it enhances disability in animals with EAE. This grant aims to clarify the function of Cystatin C using the EAE animal model as well as immune cells from MS patients.