Dataset Information
Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.
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ABSTRACT: Objective
Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor ? axis (GM-CSFR?) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFR? in RA synovial tissue and investigated the effects of anti-GM-CSFR? antibody treatment in vitro and in vivo in a preclinical model of RA.Methods
We compared GM-CSFR? expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice.Results
GM-CSFR? was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFR? positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils.Conclusions
The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.
SUBMITTER: Greven DE
PROVIDER: S-EPMC4602263 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
Publications
Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.
Annals of the rheumatic diseases 20140616 10
<h4>Objective</h4>Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA.<h4>Methods</h4>We compared GM-CSFRα expression on macrophages posit ...[more]
