Cell Trafficking Interference in Inflammatory Bowel Disease: Therapeutic Interventions Based on Basic Pathogenesis Concepts.

Abstract:

:After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effective alternative. With 2 currently approved drugs (ie, natalizumab, vedolizumab) and several others in phase 3 trials (eg, etrolizumab, ozanimod, anti-MAdCAM-1), the blockade of trafficking molecules has firmly emerged as a new therapeutic era for IBD. We discuss the targets that have been explored in clinical trials: chemokines and its receptors (eg, IP10, CCR9), integrins (eg, natalizumab, AJM300, vedolizumab, and etrolizumab), and its endothelial ligands (MAdCAM-1, ICAM-1). We also discuss a distinct strategy that interferes with lymphocyte recirculation by blocking lymphocyte egress from lymph nodes (small molecule sphingosine-phosphate receptor [S1PR] agonists: fingolimod, ozanimod, etrasimod, amiselimod). Strategies on the horizon include additional small molecules, allosteric inhibitors that specifically bind to the active integrin form and nanovectors that allow for the use of RNA interference in the quest to modulate pro-inflammatory leukocyte trafficking in IBD.

journal_name

Inflamm Bowel Dis

authors

Pérez-Jeldres T,Tyler CJ,Boyer JD,Karuppuchamy T,Bamias G,Dulai PS,Boland BS,Sandborn WJ,Patel DR,Rivera-Nieves J

doi

10.1093/ibd/izy269

subject

Has Abstract

pub_date

2019-01-10 00:00:00

pages

270-282

issue

2

eissn

1078-0998

issn

1536-4844

pii

5079145

journal_volume

25

pub_type

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