Alicaforsen therapy in inflammatory bowel disease

Abstract

Current understanding of inflammatory bowel disease (IBD) has resulted in the development of new treatments that antagonise the pathological pathways associated with T lymphocytes and inflammatory cytokines. Intercellular adhesion molecules (ICAMs) contribute to leukocyte adhesion and migration, local lymphocyte stimulation, and are responsible for T lymphocyte trafficking in the intestine. ICAMs are constitutively expressed by enterocytes and are upregulated in the presence of inflammation. Mobile T lymphocytes in the circulatory system are key to the deleterious inflammatory response resulting in IBD. Alicaforsen, a human ICAM-1 antisense oligonucleotide, blocks ICAM-1 production by disabling target RNA molecules and blocking the translation of protein. This alters the local inflammatory reaction in the intestinal wall. Alicaforsen has been evaluated in both Crohn's disease and ulcerative colitis. The role of the immune system in IBD is reviewed and the responses to treatment with alicaforsen are discussed.