Investigational C-C chemokine receptor 2 antagonists for the treatment of autoimmune diseases.
BACKGROUND
C-C chemokine receptor 2 (CCR2) antagonists belong to a group of chemokine blockers, which represent a new strategy for inflammatory diseases treatment by interfering with the complex system of chemokines and their receptors. A number of CCR2 antagonists are being developed for treatment of autoimmune diseases by different pharmaceutical and biotechnological companies.


OBJECTIVE
In this article the dark and the bright side of therapeutic CCR2 antagonism is discussed, with a view to its potential efficacy in various autoimmune diseases, in which clinical trials are already in progress, such as multiple sclerosis and rheumatoid arthritis. We describe different modes of possible interactions with CCR2-chemokine CC motif ligand 2 (CCL2) axis, usefulness of experimental animal models, continuing clinical trials and future perspectives of CCR2 antagonists.


METHODS
Until now only a few peer-reviewed articles providing data on the progress of preclinical and clinical trials with CCR2 antagonists have been published; therefore, we also present data based on preliminary reports, obtained from a number of press releases, conference communications and from the PharmaProjects database.


CONCLUSIONS
Although there is growing evidence for a great therapeutic potential of CCR2 blockade in autoimmune diseases, especially well documented in experimental animal models, so far clinical trials with CCR2 antagonists in humans have been moderately encouraging or even disappointing, indicating a need to further elucidate the complex system of chemokine interactions.
Kalinowska
Alicja
A
University of Medical Sciences, Department of Clinical Neuroimmunology by Chair of Neurology, ul. Przybyszewskiego 49, 60-355 Poznan, Poland. alicjakal@yahoo.com
Losy
Jacek
J
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011485:Protein Binding; D016896:Treatment Outcome
D018932:Chemokine CCL2