Targeting endothelial ligands: (ICAM-1/Alicaforsen, MAdCAM-1).
J Crohns Colitis. 2018 May 11;:
Authors: Reinisch W, Hung K, Hassan-Zahraee M, Cataldi F
The specific blockade of the endothelial ligands intercellular adhesion molecule-1 (ICAM-1) and mucosal addressin cell adhesion molecule (MAdCAM) involved in leukocyte recruitment to the site of inflammation as therapeutic targets in inflammatory bowel disease (IBD) has been recognized from their overexpression in the inflamed mucosa and their successful intervention in preclinical animal models. Interventions to target ICAM-1 in human IBD are confined to the ICAM-1 anti-sense oligonucleotide alicaforsen. Whereas results with parenteral formulations of alicaforsen in Crohn’s disease were largely negative, efficacy signals derived from studies with an enema formulation in ulcerative and pouchitis are promising and having lead to a FDA Fast-Track designation for the latter. A large phase III program in pouchitis is underway. Phase II studies with the anti-MAdCAM-1 antibody (SHP647) delivered positive results in ulcerative colitis and anti-inflammatory signals in Crohn’s disease. Furthermore, it was shown that SHP647 does not affect the number and composition of cells in cerebrospinal fluid suggesting that the compound is not affecting immune-surveillance in the central nervous system. Both alicaforsen and SHP647 are promising compounds also based on the clear safety profile observed so far.
PMID: 29757363 [PubMed – as supplied by publisher]