Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19303
Jüngel, A; Ospelt, C; Lesch, M; Thiel, M A; Sunyer, T; Schorr, O; Michel, B A; Gay, R E; Kolling, C; Flory, C; Gay, S; Neidhart, M (2010). Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis. Annals of the Rheumatic Diseases, 69(5):898-902.
OBJECTIVE: In the present study we evaluated the decrease of cartilage destruction by a novel orally active and specific MMP-13 inhibitor in three different animal models of rheumatoid arthritis (RA). MATERIALS AND METHODS: The SCID mouse co-implantation model of RA, collagen-induced arthritis (CIA) model in mice and the antigen induced arthritis model (AIA) in rabbits were used. RESULTS: In the SCID mouse co-implantation model this inhibitor resulted in reduced cartilage destruction by 75%. In the CIA model of RA, the MMP-13 inhibitor resulted in a significant and dose dependent decrease in clinical symptoms as well as of cartilage erosion by 38% (30 mg/kg), 28% (10 mg/kg) and 21% (3 mg/kg). No significant effects were observed in the AIA model. No toxic effects were observed in all three animal models. CONCLUSION: Although several MMPs in concert with other proteinases play a role in the process of cartilage destruction, there is a need for highly selective MMP inhibitors to reduce severe side effects that occur with non-specific inhibitors. Significant inhibition of MMP-13 reduced cartilage erosions in two out of three tested animal models of RA. These results strongly support the development of this class of drugs to reduce or halt joint destruction in patients with RA.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||17 Jun 2009 17:17|
|Last Modified:||27 Nov 2013 17:41|
|Publisher:||BMJ Publishing Group|
|Citations:||Web of Science®. Times Cited: 15|
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