A Novel Tolerance Therapeutic for Treating Multiple Sclerosis

Our goal is to develop VTC MSas a novel tolerance inducing therapeutic to treat Multiple SclerosisMSMS is the most common demyelinating disorder of the Central Nervous SystemCNSaffecting approximatelymillion people worldwide andin the US aloneCurrent 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 causeFor successful induction of immune tolerancemucosal tissues play a significant roleThe epithelial layers that cover the Gut Associated Lymphoid TissueGALTand Nasopharyngeal Associated Lymphoid TissueNALTareas contain a subpopulation of specialized cellsmicrofold or M cellswhich sample environmental antigens and present them to the adjacent immune cellsA number of studies now confirm that these cells play a crucial role in the generation of tolerance to a given antigenReoviruses are segmenteddoublestranded RNA viruses that bind and infect humans via mucosal surfaces using the viral coat proteinpWe have demonstrated that fusion proteins consisting of pfused to an antigen of choice can bind to M cells and generate a tolerigenic immune response to that antigenThe ability of pantigen targeting to induce tolerance has been studied in both allergy and autoimmune modelsincluding the mouse EAE model of MSusing both oral and intranasal dosing routesThese studies demonstrate that pmediated tolerance to the MS auto antigenMOGbut not recombinant MOG aloneentirely prevents CNS pathology and clinical manifestation of EAEThe tolerance response is antigen specificand due to the induction of antiinflammatory cytokines and an increase in suppressive regulatory T cellsTregsThe goal of this Fast track SBIR application is to develop VTC MSas an orally administeredtolerance therapeutic for the treatment of MSVTC MSis a recombinant protein consisting of pfused to three of the major MS autoantigensmyelin oligodendrocyte glycoproteinMOGmyelin basic proteinMPBand antigenic regions of proteolipid proteinPLPThis design allows VTC MSto exploit ptargeting of MS auto antigens specifically to M cellsand to induce tolerance to a broad array of antigenic epitopes within these antigensThe key objectives are toestablish VTC MSproduction and analytical assays to support manufacturingpurificationbioactivity determinationand formulationdefine the IND enabling studies to support our clinical study designanddevelop non GLP and GLP preclinical datasets to help us obtain FDA IND approvalSuccessful commercialization of VTC MSwould ultimately provide a profound front line medical advancement in the treatment of MS