Drug Discovery Approaches for Inflammatory Bowel Disease

Abstract

New biologics, such as specific IL-23 and sphingosine-1-phosphate (S1P) receptor antibodies, are being developed as potential therapeutic options for patients with inflammatory bowel disease (IBD). These antibodies have demonstrated efficacy in murine models of colitis, which mimic to some degree human IBD. Other specific biologics are being developed related to pertinent targets for ulcerative colitis, such as IL-9 and IL-13. Antibodies are also being developed, which target other pertinent pro-inflammatory cytokines (IL-6 and GM-CSF). In terms of biologic drug discovery, the concept of T-cell plasticity should be taken into account. Th17 cells can shift into a Th1 phenotype, in the presence of cytokines like IL-12 and TNF-α, during the pathogenesis of Crohn's disease. These Th17 derived Th1 cells have been named non-classic Th1 cells. Notably, one of the key cytokines produced by these cells is GM-CSF. Developing an enhanced understanding of T-cell plasticity will aid in the development of better biologics for IBD during the 21st century.