Antibody mediated targeting of autoimmune cells in multiple sclerosis

Abstract

Multiple Sclerosis (MS) is a debilitating autoimmune disorder of the central nervous system (CNS) affecting over 77,000 Canadians, with a prevalence rate of almost one out of 300 Canadians, with the highest rates in Saskatchewan. Myelination of neuronal axons is essential for the normal and rapid electrical conduction along an axon. Currently there are few feasible options to treat MS. Here, we propose a novel therapy that specifically targets aberrant immune cells.We created a trimolecular peptide (TPC) that combines and antigen sequence (myelin oligodendrocyte glycoprotein; MOG 35‐55), a modified type IV secretatory system (TIVSS) peptide, and an apoptotic protein. As the TPC displays MOG, the TPC is hypothesized to only bind to immune cells that are actively seeking MOG (e.g. in MS). Since the TPC contains TIVSS, the cell that bound the antigen (e.g. MOG 35‐55) is forced to take up the TPC. Lastly, the apoptotic protein, which is now inside the cell, causes the cell to undergo apoptosis. Thus eliminating the aberrant cell.In order to test this TPC compound, we induced experimental autoimmune encephalopathy (EAE) using MOG 35‐55. Test compound was administered 15 days post EAE induction. Administration of the TPC resulted in the suppression of autoimmune cells, as determined via flocytometry. We also found significant improvements in motor function as well as a reduction in MS plaque formation in the cerebellum. By targeting the pathogenic immune response whilst leaving the patient’s normal immune response intact, we believe this strategy will lead to improved clinical outcomes without the side effects seen in current MS therapies.Support or Funding InformationSaskatchewan Health Research Foundation