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Animal models for arthritis: innovative tools for prevention and treatment
  1. George Kollias1,
  2. Piyi Papadaki1,
  3. Florence Apparailly2,
  4. Margriet J Vervoordeldonk3,
  5. Rikard Holmdahl4,
  6. Vera Baumans5,
  7. Christian Desaintes6,
  8. James Di Santo7,
  9. Jörg Distler8,
  10. Paul Garside9,
  11. Martin Hegen10,
  12. Tom W J Huizinga11,
  13. Astrid Jüngel12,
  14. Lars Klareskog13,
  15. Iain McInnes9,
  16. Ioannis Ragoussis14,
  17. Georg Schett8,
  18. Bert ‘t Hart15,
  19. Paul P Tak3,
  20. Rene Toes11,
  21. Wim van den Berg16,
  22. Wolfgang Wurst17,
  23. Steffen Gay12
  1. 1Biomedical Sciences Research Center ‘Alexander Fleming’, Institute of Immunology, Vari-Athens, Greece
  2. 2INSERM U844, Montpellier, France
  3. 3Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, The Netherlands
  4. 4Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
  5. 5Department of Animals, Science and Society, Division of Laboratory Animal Science, University of Utrecht, Utrecht, The Netherlands
  6. 6DG Research, Health, Infectious diseases European Commission, Brussels, Belgium
  7. 7Cytokines and Lymphoid Development Lab, Department of Immunology, Pasteur Institute, Paris, France
  8. 8Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
  9. 9Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK
  10. 10Pfizer, Cambridge, Massachusetts, USA
  11. 11Center of Experimental Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  12. 12Department of Rheumatology, University Hospital Zürich, Zurich, Switzerland
  13. 13Rheumatology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden
  14. 14The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  15. 15Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands
  16. 16Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  17. 17Institute of Developmental Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, Technical University Munich, Munich, Germany
  1. Correspondence to George Kollias, Biomedical Sciences Research Center ‘Alexander Fleming’, 34 Fleming Street, 16672 Vari-Athens, Greece; g.kollias{at}fleming.gr

Abstract

The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive ‘pathogenesis map’ that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in ‘omics’ profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology.

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Footnotes

  • Funding European League Against Rheumatism (EULAR).

  • Competing interests None.

    This report has been prepared by the European League Against Rheumatism (EULAR) Study Group on Animal Models as a guidance document to provide recommendations on current bottlenecks and limitations in predictive RA animal modelling and to guide future directions that will enhance innovation in preclinical research following a workshop organised at the EULAR House in Zurich on 18–19 March 2010.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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