A Novel Tolerance Therapeutic for Treating Multiple Sclerosis

DESCRIPTION provided by applicant Our goal is to develop VTC MS as a novel tolerance inducing therapeutic to treat Multiple Sclerosis MS MS is the most common demyelinating disorder of the Central Nervous System CNS affecting approximately million people worldwide and in the US alone Current and developing treatment of MS relies mainly on immuno suppression and modulation to reduce inflammatory symptoms creating a significant need for new therapeutics that treat the underlying cause For successful induction of immune tolerance mucosal tissues play a significant role The epithelial layers that cover the Gut Associated Lymphoid Tissue GALT and Nasopharyngeal Associated Lymphoid Tissue NALT areas contain a subpopulation of specialized cells microfold or M cells which sample environmental antigens and present them to the adjacent immune cells A number of studies now confirm that these cells play a crucial role in the generation of tolerance to a given antigen Reoviruses are segmented doublestranded RNA viruses that bind and infect humans via mucosal surfaces using the viral coat protein p We have demonstrated that fusion proteins consisting of p fused to an antigen of choice can bind to M cells and generate a tolerigenic immune response to that antigen The ability of p antigen targeting to induce tolerance has been studied in both allergy and autoimmune models including the mouse EAE model of MS using both oral and intranasal dosing routes These studies demonstrate that p mediated tolerance to the MS auto antigen MOG but not recombinant MOG alone entirely prevents CNS pathology and clinical manifestation of EAE The tolerance response is antigen specific and due to the induction of antiinflammatory cytokines and an increase in suppressive regulatory T cells Tregs The goal of this Fast track SBIR application is to develop VTC MS as an orally administered tolerance therapeutic for the treatment of MS VTC MS is a recombinant protein consisting of p fused to three of the major MS autoantigens myelin oligodendrocyte glycoprotein MOG myelin basic protein MPB and antigenic regions of proteolipid protein PLP This design allows VTC MS to exploit p targeting of MS auto antigens specifically to M cells and to induce tolerance to a broad array of antigenic epitopes within these antigens The key objectives are to establish VTC MS production and analytical assays to support manufacturing purification bioactivity determination and formulation define the IND enabling studies to support our clinical study design and develop non GLP and GLP preclinical datasets to help us obtain FDA IND approval Successful commercialization of VTC MS would ultimately provide a profound front line medical advancement in the treatment of MS PUBLIC HEALTH RELEVANCE Multiple sclerosis MS is the most common demyelinating disorder of the CNS affecting approximately million people worldwide Currently the most effective therapies to treat MS work through immune system modulation to suppress the inflammatory response This project aims to develop a novel antigen specific tolerance therapeutic VTC MS for the treatment of MS VTC MS is expected to rapidly induce long term tolerance to the major MS auto antigens following low dose oral short term treatment Successful commercialization of VTC MS would ultimately provide a profound front line medical advancement in the treatment of MS