Article Text

other Versions

PDF
Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis
  1. Astrid Jüngel (astrid.juengel{at}usz.ch)
  1. Experimental Rheumatology, Switzerland
    1. Caroline Ospelt (caroline.ospelt{at}usz.ch)
    1. Center of Experimental Rheumatology, Switzerland
      1. Mark Lesch (mark.lesch{at}pfizer.com)
      1. Pfizer Inc., United States
        1. Melissa Thiel (melissa.thiel{at}pfizer.com)
        1. Pfizer Inc., United States
          1. Teresa Sunyer (teresa.sunyer{at}pfizer.com)
          1. Pfizer Inc., United States
            1. Olivier Schorr (schorrolivier{at}gmx.ch)
            1. Center of Experimental Rheumatology, Switzerland
              1. Beat A Michel (beat.michel{at}usz.ch)
              1. University Zurich, Switzerland
                1. Renate E Gay (renate.gay{at}usz.ch)
                1. Experimental Rheumatology, Switzerland
                  1. Christoph Kolling (christoph.kolling{at}kws.ch)
                  1. Schulthess Clinic, Switzerland
                    1. Craig Flory (craig.flory{at}pfizer.com)
                    1. Pfizer Inc., United States
                      1. Steffen Gay (steffen.gay{at}usz.ch)
                      1. Experimental Rheumatology, Switzerland
                        1. Michel Neidhart (michel.neidhart{at}usz.ch)
                        1. Experimental Rheumatology, Switzerland

                          Abstract

                          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).

                          Material 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.

                          Statistics from Altmetric.com

                          • Web Only Data ard.2008.106021

                            Files in this Data Supplement:

                          Request permissions

                          If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.