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Technology Insight: gene transfer and the design of novel treatments for rheumatoid arthritis

Nature Clinical Practice Rheumatology volume 2, pages 153–162 (2006)Cite this article

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by systemic inflammation and joint destruction. Novel therapies have emerged during the past decade, marking a new era in the treatment of RA. Meanwhile, in vivo and in vitro gene-transfer studies have provided valuable insights into mechanisms of disease pathogenesis. Advanced gene-delivery techniques and animal models promise further progress in RA research and the development of novel therapeutic strategies for this disease. In this article we provide an overview of the wide spectrum of potential targets that have been identified so far, discuss currently available gene-transfer methods, and outline the barriers that need to be overcome for these approaches to be successfully applied in daily practice.

Key Points

  • Cytokines, activating factors of synovial cells, matrix-degrading enzymes and regulators of cell survival and apoptosis have been characterized as potential therapeutic targets in rheumatoid arthritis (RA)

  • Gene-transfer experiments in animal models have been useful for the identification of disease-relevant molecules

  • The severe combined immunodeficient mouse co-implantation model is currently the most informative model for the investigation of cytokine-independent processes in RA

  • The first clinical gene-transfer studies in RA patients have been conducted and the results are available

  • A variety of risks and technical hurdles need to be overcome before gene-transfer approaches can become established as therapies for RA

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Figure 1: Simplified illustration of the Tet-On system.
Figure 2: The system based on complement factor 3 promoter and HIV transactivator of transduction protein.
Figure 3: The severe combined immunodeficient mouse co-implantation model.

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Acknowledgements

The work is partially funded by the Articulum Fellowship Program provided by Pfizer as well as by the Swiss National Science Foundation.

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Author notes

  1. F Moritz is a Medical Postdoctoral Fellow, O Distler is a Senior Fellow and Research Group Leader and C Ospelt is a Medical Postdoctoral Fellow

Authors and Affiliations

  1. the Center of Experimental Rheumatology at the University of Zurich,

    Falk Moritz, Oliver Distler & Caroline Ospelt

  2. Chief of Staff at the Dean's Office of the School of Medicine at the University of Zurich,

    Renate E Gay

  3. Head of the Center of Experimental Rheumatology at the University of Zurich and is Director of the World Health Organization Collaborating Center for Molecular Biology and Novel Strategies for the Treatment of Rheumatic Diseases, Zurich, Switzerland

    Steffen Gay

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  1. Falk Moritz
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Correspondence to Steffen Gay.

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Moritz, F., Distler, O., Ospelt, C. et al. Technology Insight: gene transfer and the design of novel treatments for rheumatoid arthritis. Nat Rev Rheumatol 2, 153–162 (2006). https://doi.org/10.1038/ncprheum0117

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