No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3

R Reuss1, V Schreiber, A Klein

  • 1Department of Neurology, Justus Liebig University, Giebetaen Germany. reinhard.reuss@neuro.med.uni-giessen.de

Multiple Sclerosis (Houndmills, Basingstoke, England)
|January 21, 2010
PubMed

Insights

This study examined intercellular adhesion molecules in multiple sclerosis patients treated with BX 471. While ICAM-3 expression trended higher in treated patients, no significant differences were found compared to placebo.

Area of Science:

  • Immunology
  • Neuroscience
  • Pharmacology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • Intercellular adhesion molecules (ICAMs) play a role in immune cell trafficking and inflammation.
  • Chemokine receptors are implicated in the pathogenesis of MS.

Purpose of the Study:

  • To investigate the effect of the chemokine receptor 1 antagonist BX 471 on ICAM-1 and ICAM-3 expression in patients with relapsing-remitting MS.
  • To assess changes in ICAM expression during and after a 16-week treatment period.

Main Methods:

  • A randomized, double-blind, placebo-controlled phase II study involving 34 relapsing-remitting MS patients.
  • Oral administration of BX 471 or placebo for 16 weeks.
  • Flow cytometry was used to measure ICAM-1 and ICAM-3 expression on peripheral blood mononuclear cells (PBMCs).
  • Statistical analysis included multivariate analysis of variance and Mann Whitney U test.

Main Results:

  • A trend towards increased ICAM-3 expression was observed on CD14(+) PBMCs in the BX 471 (verum) group during therapy.
  • No statistically significant differences in ICAM-1 or ICAM-3 expression were found between the verum and placebo groups.
  • The observed trend in ICAM-3 expression is likely a minor epiphenomenon due to receptor cross-talk.

Conclusions:

  • The chemokine receptor 1 antagonist BX 471 did not significantly alter ICAM-1 or ICAM-3 expression in relapsing-remitting MS patients.
  • Further research is needed to fully elucidate the role of ICAMs and chemokine receptors in MS pathogenesis and treatment.