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Gene Therapy for Restenosis

Current Status

Drugs volume 62, pages 1575–1585 (2002)Cite this article

Abstract

Atherosclerosis is a major cause of morbidity and mortality in Western world. Vascular occlusion caused by atherosclerosis usually requires invasive treatment, such as surgical bypass or angioplasty However, bypass graft failure and restenosis limit the usefulness of these procedures, with 20% of patients needing a new revascularisation procedure within 6 months of angioplasty. Numerous pharmacological agents have been investigated for the prevention of restenosis but none has shown undisputed efficacy in clinical medicine.

Gene transfer offers a novel approach to the treatment of restenosis because of easy accessibility of vessels and already existing gene delivery methods. It can be used to overexpress therapeutically important proteins locally without high systemic toxicity, and the therapeutic effect can be targeted to a particular pathophysiological event. Promising results have been obtained from many pre-clinical experiments using therapeutic genes or oligonucleotides to prevent restenosis. Early clinical trials have shown that plasmid- and adenovirus-mediated vascular gene transfers can be conducted safely and are well tolerated. Ex vivo gene therapy with E2F-decoy succeeded in reducing graft occlusion rate after surgical bypass in a randomised, double-blind clinical trial.

In the future, further development of gene delivery methods and vectors is needed to improve the efficacy and safety of gene therapy. Also, better knowledge of vascular biology at the molecular level is needed to find optimal strategies and gene combinations to treat restenosis. Provided that these difficulties can be solved, gene therapy offers an enormous potential for clinical medicine in the future.

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Acknowledgements

This study was supported by grants from Finnish Academy and Sigrid Juselius Foundation.

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Affiliations

  1. Department of Molecular Medicine, A. I. Virtanen Institute, University of Kuopio, P.O. Box 1627, Kuopio, FIN-70211, Finland

    Juha Rutanen, Johanna Markkanen &  Seppo Ylä-Herttuala

  2. Department of Medicine, Kuopio University Hospital, Kuopio, Finland

    Seppo Ylä-Herttuala

  3. Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

    Seppo Ylä-Herttuala

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  1. Juha Rutanen
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  3. Seppo Ylä-Herttuala
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Rutanen, J., Markkanen, J. & Ylä-Herttuala, S. Gene Therapy for Restenosis. Drugs 62, 1575–1585 (2002). https://doi.org/10.2165/00003495-200262110-00001

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Keywords

  • Vascular Endothelial Growth Factor
  • Gene Therapy
  • Gene Transfer
  • Neointimal Hyperplasia
  • Gene Transfer Method