Development of a Novel Therapeutic for Hyperthyroidism

GravesdiseaseGDis the most common cause of hyperthyroidism and is caused by stimulation of the thyroid stimulating hormone receptorTSHRby thyroid receptor stimulating antibodiesTSAbsTreatment of GD involves antithyroid medication therapyradioactive iodineand surgeryAt the presentfew alternative forms of therapy for GD are available or are in developmentThe ability to block TSHR action may also be of benefit to other conditionsincluding GravesorbitopathyGOand differentiated thyroid cancerThusthere is considerable interest in developing novel treatments to block TSHR actionRecombinant adenoassociated virusrAAVtherapy has been developed as a viral vector for gene therapySeveral of these clinical trials have taken place at the University of FloridaUFwhich is a major center for the study of AAVbased gene therapyOf the different rAAV that the serotypes that are availablerAAVis the preferred vector for vector mediated immunotherapy studies in rodent modelsAlthough vector based immunotherapy has been proposed for infectious diseaseswe such approaches that target antibody mediated conditions are limitedIn preliminary studieswe identified a commercially available monoclonal antibody that blocks TSAb and thyroid stimulating hormoneTSHactionWe also developed a rAAVconstruct that expresses this functional antibodyThuswe hypothesize that the rAAVTBAb vector we generated will target and block TSHR activationIn this PhaseSTTR proposalwe will evaluate the utility of our new therapeutic in blocking TSH receptor activationIn SAwe will test the ability of our therapeutic to block the action of TSH in single dose and multidose studiesIn SAwe will test the ability of our vector to block the activity of administered TSAbs and a validated murine model of GDTo achieve these goalsour team will include experts in thyroidology and rAAV biology and will involve collaborative efforts of the University of Florida and Medosome Biotec LLCWe anticipate that the discovery of this novel therapeutic approach to inhibit thyroid production and block TSAbs will be of considerable clinical importance and commercial potential Gravesandapos s disease is a debilitating endocrine conditionwhich rarely spontaneously resolvesand is treated by medical therapysurgeryor radioactive iodineAt presentthere are few alternative treatments for this conditionThe goal of this work is to develop a novel therapeutic approach for this condition using adenoassociated virusAAVto express TSH receptor blocking antibodiesThis approach may also have utility for the treatment of Gravesandaposorbitopathy and thyroid cancer