Antisense inhibition of ICAM-1 expression as therapy provides insight into basic inflammatory pathways through early experiences in IBD

Abstract

Background: Alicaforsen (ISIS 2302), an antisense to intercellular adhesion molecule-1 (ICAM-1) (CD54), was designed to inhibit ICAM-1 expression. ICAM-1 seems to play a role in cell-mediated inflammation, specifically cell trafficking. For this reason, it may be useful in a variety of immune-mediated diseases, including inflammatory bowel disease. Objective: To evaluate the use of alicaforsen in clinical trials to understand its efficacy and side effects, as well as assess for evidence that may offer insight into disease pathways. Methods: We evaluate all of the available, published trials, with a focus on the prospective, randomized trials. Results/conclusions: Systemic treatment for Crohn's disease has not revealed significant effect. Topical enemas for ulcerative colitis have demonstrated some effect in secondary outcomes, and initial studies in pouchitis are promising. In general, the compound has been well tolerated and safe.

Keywords::

• alicaforsen
• antisense oligodeoxyribonucleotides
• Crohn's disease
• ICAM-1
• immunosuppressive agents
• inflammatory bowel disease
• ISIS 2302
• pouchitis
• ulcerative colitis