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EULAR Standing Committee of Investigative Rheumatology: report of activities 2002–3
  1. C Jorgensen
  1. Chairman of the Gene Therapy Work Group

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    GENE THERAPY STUDY GROUP

    The Work Group on Gene Therapy in Arthritis presented data in Marseille, 27 February 2003. The group is active, with a high quality of scientific exchange, as the field of gene therapy is changing. One major limitation for the clinical application of gene therapy in joint diseases is the safety of the procedure and the available vectors. The gene therapy trial conducted on 11 SCID children was shortened because of leukaemia induced by the vector. The oncogene activation was shown to be related to the mutagenesis induced by the retroviral vector. Thus we need to improve our vectors before planning any clinical trial in rheumatoid arthritis.

    Two area of research are open: viral vectors, with long term expression, and non-viral technology. The most widely used viral vectors are adenoviruses, but these are limited by their non-specific inflammation, and retroviruses. The most promising vectors are lentiviral derived or recombinant adeno-associated viruses (rAAV). Professor Tak’s team presented recent data on new rAAV serotypes that might be more efficient for synoviocyte transfection. However, the diffusion of these vectors after intra-articular injection remains to be determined. Dr Apparailly from Montpellier reported results concerning non-viral inducible and tightly regulated cytokine expression. She used electroporation in vivo in the muscle to obtain sustained IL10 expression. This technology improved inflammation in the collagen induced arthritis model. A second approach to restore immune homoeostasis is to use genetically modified dendritic cells. Dr Tarner from Regensburg demonstrated elegantly the homing of these cells to the inflamed paws using a cooled CDD camera in arthritic animals. He was able to show in vivo that the homing to the joints after IV injection of dendritic cells was specific to type II collagen.

    To improve our knowledge we decided to share a common database with the available vectors, plasmids, promoters, cell lineage, or animal models. All laboratories interested in this European collaboration will have access to these tools. This constitutes the first step for a European collaborative network. We will apply within the call of the 6FP programme from the EU community for a Network of Excellence, and Thomas Pap will coordinate this initiative. An international meeting in the field of cell and gene therapy in bone and joint disorders will be organised in May 2004 after the success of the meeting in Montpellier. It was suggested that this workshop would be held in Amsterdam, and we hope the participants will joint us for a discussion of innovative and advanced technology in arthritis.

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