Gene transfer to human joints: progress toward a gene therapy of arthritis.

@article{Evans2005GeneTT,
  title={Gene transfer to human joints: progress toward a gene therapy of arthritis.},
  author={C. Evans and P. Robbins and S. Ghivizzani and M. Wasko and M. Tomaino and R. Kang and Thomas A Muzzonigro and M. Vogt and E. Elder and T. Whiteside and Simon C Watkins and J. Herndon},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2005},
  volume={102 24},
  pages={
          8698-703
        }
}
  • C. Evans, P. Robbins, +9 authors J. Herndon
  • Published 2005
  • Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
This article describes the clinical application of gene therapy to a nonlethal disease, rheumatoid arthritis (RA). Intraarticular transfer of IL-1 receptor antagonist (IL-1Ra) cDNA reduces disease in animal models of RA. Whether this procedure is safe and feasible in humans was addressed in a phase I clinical study involving nine postmenopausal women with advanced RA who required unilateral sialastic implant arthroplasty of the 2nd-5th metacarpophalangeal (MCP) joints. Cultures of autologous… Expand
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Rheumatoid arthritis (RA) is an autoimmune disease affecting nearly 1% of the population. The joints of RA patients become inflamed and a pannus of synovial tissue invades cartilage and destroysExpand
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Abstract Arthritis gene therapy has its origins in research conducted at the University of Pittsburgh in the late 1980s. This was based on the concept of using gene transfer to intra-articularExpand
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A newly published phase I clinical trial of a gene therapy approach to treating rheumatoid arthritis (RA) indicates that therapeutic genes can be transferred safely to, and be expressed in,Expand
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OBJECTIVES Gene therapy using cells as vectors to achieve secretion of therapeutic proteins may hold promise in the treatment of chronic diseases. Cell-based gene therapy with xenogeneic cellsExpand
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In recent years, significant progress has been made in the treatment of rheumatoid arthritis (RA). In addition to conventional therapy, novel biologicals targeting tumour necrosis factor-alpha haveExpand
Gene therapy as a therapeutic approach for the treatment of rheumatoid arthritis: innovative vectors and therapeutic genes.
In recent years, significant progress has been made in the treatment of rheumatoid arthritis (RA). In addition to conventional therapy, novel biologicals targeting tumour necrosis factor-alpha haveExpand
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Findings provide experimental evidence for the feasibility of antiinflammatory gene therapy for arthritis by finding that gene transfer of sIL-1ra significantly suppressed the severity of recurrence of arthritis, as assessed by measuring joint swelling and by the gross-observation score. Expand
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Results indicate that lentiviral vectors are capable of efficient in vivo gene transfer to synovium and merit further investigation as a means of providing long-term expression for gene-based treatments of arthritis. Expand
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Knee joints expressing human IRAP were protected from the leukocytosis that otherwise follows the intraarticular injection of recombinant human interleukin 1 beta and the feasibility of treating arthritis and other joint disorders with gene therapy is demonstrated. Expand
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TLDR
A novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques is described. Expand
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Intra-articular delivery of LV-hIL-1Ra strongly prevented swelling in all treated knees, even in those receiving the greatest dose of IL-1beta(+) cells, and cellular infiltration, cartilage erosion, and invasiveness of inflamed synovium were effectively prevented in LV- hIL- 1Ra-treated knees and were significantly inhibited in contralateral joints. Expand
Direct adenoviral gene transfer of viral IL-10 to rabbit knees with experimental arthritis ameliorates disease in both injected and contralateral control knees.
TLDR
The results suggest that direct, local intraarticular delivery of the vIL-10 gene may have polyarticular therapeutic effects, as well as the degree of synovitis, while maintaining high levels of cartilage matrix synthesis. Expand
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