Darren L Asquith1, Steven A Bryce, Robert J B Nibbs. 1. Centre for Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
Abstract
PURPOSE OF REVIEW: To provide an update of past failures, future prospects and key challenges facing the therapeutic targeting of chemokines and their receptors in rheumatoid arthritis. RECENT FINDINGS: Clinical trials in rheumatoid arthritis have been undertaken with small molecule antagonists or neutralizing antibodies targeting CCR1, CCR5 and CXCL10. Some encouraging results have emerged. Laboratory and clinical research has identified CCL19, CXCL13 and CXCL12, and their receptors, as potential future targets. Developments in our appreciation of posttranslational chemokine modification highlight the complexity of chemokine networks operating in inflamed tissues, and the substantial gaps in existing knowledge. SUMMARY: Despite previous disappointments, there are still reasons to be optimistic that drugs targeting chemokines and their receptors could be developed for the treatment of rheumatoid arthritis. However, a deeper understanding of the chemokine networks at work in inflamed joints is a necessary prerequisite.
PURPOSE OF REVIEW: To provide an update of past failures, future prospects and key challenges facing the therapeutic targeting of chemokines and their receptors in rheumatoid arthritis. RECENT FINDINGS: Clinical trials in rheumatoid arthritis have been undertaken with small molecule antagonists or neutralizing antibodies targeting CCR1, CCR5 and CXCL10. Some encouraging results have emerged. Laboratory and clinical research has identified CCL19, CXCL13 and CXCL12, and their receptors, as potential future targets. Developments in our appreciation of posttranslational chemokine modification highlight the complexity of chemokine networks operating in inflamed tissues, and the substantial gaps in existing knowledge. SUMMARY: Despite previous disappointments, there are still reasons to be optimistic that drugs targeting chemokines and their receptors could be developed for the treatment of rheumatoid arthritis. However, a deeper understanding of the chemokine networks at work in inflamed joints is a necessary prerequisite.
Authors: Yun Deng; Jian Zhao; Daisuke Sakurai; Andrea L Sestak; Vadim Osadchiy; Carl D Langefeld; Kenneth M Kaufman; Jennifer A Kelly; Judith A James; Michelle A Petri; Sang-Cheol Bae; Marta E Alarcón-Riquelme; Graciela S Alarcón; Juan-Manuel Anaya; Lindsey A Criswell; Barry I Freedman; Diane L Kamen; Gary S Gilkeson; Chaim O Jacob; Joan T Merrill; Patrick M Gaffney; Kathy Moser Sivils; Timothy B Niewold; Rosalind Ramsey-Goldman; John D Reveille; R Hal Scofield; Anne M Stevens; Susan A Boackle; Luis M Vilá; I I Woong Sohn; Seung Lee; Deh-Ming Chang; Yeong Wook Song; Timothy J Vyse; John B Harley; Elizabeth E Brown; Jeffrey C Edberg; Robert P Kimberly; Rita M Cantor; Bevra H Hahn; Jennifer M Grossman; Betty P Tsao Journal: Ann Rheum Dis Date: 2016-01-18 Impact factor: 19.103
Authors: Douglas P Dyer; Catherina L Salanga; Scott C Johns; Elena Valdambrini; Mark M Fuster; Caroline M Milner; Anthony J Day; Tracy M Handel Journal: J Biol Chem Date: 2016-04-04 Impact factor: 5.157