Poster abstracts

Poster number 105 submitted by Kevin Peine

Treatment of Experimental Autoimmune Encephalomyelitis by Co-Delivery of Disease Associated Peptide and Dexamethasone in Acetalated Dextran Microparticles

Kevin J. Peine (Molecular Cellular and Developmental Biology, The Ohio State University), Mireia Guerau-de-Arellano, Priscilla W. Lee, Mary Severin, Haiyan Peng (College of Medicine, The Ohio State University), Naveen Kanthamnenthi (Department of Pharmaceutics, The Ohio State University), Yuhong Yang, Amy E. Lovett-Racke (College of Medicine, The Ohio State University), Eric M. Bachelder, Kristy M. Ainslie (Department of Pharmaceutics, The Ohio State University)

Abstract:
Multiple Sclerosis (MS) is an immune-mediated, demyelinating disease of the central nervous system that causes severe neurological deficits and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments for MS suppress the immune system without antigen specificity, increasing the risks of cancer, chronic infection and other long-term side-effects. In this study, we developed an antigen specific treatment of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, by co-encapsulating the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM) into acetalated dextran (Ac-DEX) microparticles (MPs) (MOG/DXM/MPs). DXM-encapsulated MPs (DXM/MPs) reduced nitric oxide and IL-6 production by activated antigen-presenting cells, verifying that these microparticles MPs can effective deliver DXM to the cells that drive T cell activation. Clinical scores of the mice were reduced from 3.4 to 1.6 after 3 injections 3 days apart with DXM/MOG/MPs (MOG 17.6 µg and DXM 8 µg). This change in clinical score was significantly greater than observed with PBS, empty MPs, free DXM and MOG, DXM/MPs and MOG/MPs. Additionally, treatment with MOG/DEX/MPs significantly inhibited disease-associated T cell cytokine expression in an antigen-specific manner. Here we show a promising approach for the therapeutic treatment of MS using a polymer-based microparticle delivery platform to reduce myelin antigen-specific T cell responses.

Keywords: Immunomodulation, Polymeric Microparticles, Multiple Sclerosis