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Progress and prospects: hurdles to cardiovascular gene therapy clinical trials

Gene Therapy volume 18, pages 743–749 (2011)Cite this article

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Abstract

Several gene therapy approaches have been designed for the treatment of cardiovascular diseases. A positive finding is that the safety of cardiovascular gene therapy has been excellent even in long-term follow-up. However, several hurdles to this field are still present. A major disappointing feature of the trials is that while preclinical and uncontrolled phase-I gene therapy trials have been positive, none of the randomized controlled phase-II/III cardiovascular gene therapy trials have shown clinically relevant positive effects. Low gene transfer efficiency seems to be associated with several trials. A sophisticated efficient delivery method for cardiovascular applications is still lacking and only low concentrations of the gene product are produced in the target tissues. Only a few gene therapy vectors can be produced in large scale. In addition, inflammatory reactions against vectors and inability to regulate gene expression are still present. Furthermore, a strong placebo effect is affecting the results in gene therapy trials, and long-term trials have become more difficult to conduct because of the multiplicity of therapies applied simultaneously on the patients. This review summarizes advances and obstacles of current cardiovascular clinical gene therapy trials.

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Abbreviations

FGF:

fibroblast growth factor

VEGF:

vascular endothelial growth factor

CAD:

coronary artery disease

CCS:

Canadian Cardiovascular Society

AAV:

adeno-associated virus

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Acknowledgements

These studies were supported by the Academy of Finland, European Union Clinigene project (LSHB-CT-2006-018933), Finnish Foundation for Cardiovascular Research and EVO-grant (EVO5130) from Kuopio University Hospital.

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Authors and Affiliations

  1. Heart Center, Kuopio, Finland

    M Hedman, J Hartikainen & S Ylä-Herttuala

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

    J Hartikainen & S Ylä-Herttuala

  3. Department of Biotechnology and Molecular Medicine, AI Virtanen Institute, University of Eastern Finland, Kuopio, Finland

    S Ylä-Herttuala

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Correspondence to S Ylä-Herttuala.

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Hedman, M., Hartikainen, J. & Ylä-Herttuala, S. Progress and prospects: hurdles to cardiovascular gene therapy clinical trials. Gene Ther 18, 743–749 (2011). https://doi.org/10.1038/gt.2011.43

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