New Th Selective Immunomodulators for Inflammatory Disorders

PROJECT SUMMARY Inflammatory bowel disease IBD is a major group of inflammatory conditions of the colon and small intestine and about million people in the United States suffer from IBD Crohnandapos s disease and ulcerative colitis are the two clinically distinct principal types of IBD the former happens in any part of the gastrointestinal track from mouth to anus whereas the latter primarily affects the colon and the rectum While the exact cause of IBD is not fully understood hereditary genetics and environmental factors contribute to the disease development Currently there is no cure for IBD and remission may not be possible or prolonged Standard of care includes surgery and medications Acute treatment uses medications to treat infection by antibiotics and reduce inflammation by aminosalicylate anti inflammatory drugs or corticosteroids Immunomodulators and anti inflammation antibodies are the latest therapies for IBD patients who donandapos t respond well to conventional therapy However due to serious side effects non specific immune suppressors including corticosteroids are not used for long term treatment Thus new therapy is urgently needed for better treatment of IBD Recently we have discovered novel small molecule chemical agents capable of selectively inhibiting over development of pro inflammatory Th cells in mice but not other T helper subsets that have different immune functions Th cells have been recently recognized as a major driving factor for the pathogenesis of IBD In this project we will validate the therapeutic potential of our new Th immunomodulators as more effective and safer treatment for chronic inflammatory disorders such as IBD We will accomplish two Specific Aims in the Phase I of this project which are to develop highly potent and selective inhibitors that block Th cell development The Phase I results will prepare us for a more efficient Phase II study of an extensive pre clinical evaluation of our most promising drug candidates in future human clinical trials PROJECT NARRATIVE Inflammatory bowel disease IBD is one of the most prevalent inflammatory disorders affecting million people in the United States and current treatment options are limited We recently discovered novel small molecule chemical agents that selectively inhibit over development of pro inflammatory Th cells that are regarded as a major driving factor for the pathogenesis of IBD In this project we will validate the therapeutic potential of our new Th immunomodulators as more effective and safer treatment for chronic inflammatory disorders such as IBD