Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central (CNS) nervous system. While its etiology remains unknown, it is considered to be the result of an auto-inflammatory reaction targeting oligodendrocytes (ODCs), the myelin producing cells of the CNS. Current approved therapies rely on general immunosuppression, leading to a wide range of side effects. Evidence in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, suggests that antigen-specific tolerance induction might be effective in the treatment of MS.
These approaches have proven difficult to translate to the clinic, largely because the target antigens in individual MS patients remain unknown. Additionally, phenomena such as epitope spreading, in which the specificity of the autoreactive immune response shifts to different epitopes during the disease course, and HLA diversity further complicate the matter. In this project we aim to induce long-term tolerance against both immunodominant and subdominant ODCderived antigens. The proteome mixture required for this will be prepared from cultured ODCs, originating from oligospheres and (more interestingly from a translational point of view) from induced pluripotent stem cells. Our tolerogenic approach will be evaluated in different EAE models, in particular EAE induced by polyantigenic spinal cord extracts. This model mimics MS in patients in a sense that the primary disease-causing antigen is unknown.