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  • Letter to the Editor
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Reply to Bridges

Gene Therapy volume 17, pages 565–566 (2010)Cite this article

We read the recent Letter to the Editor by Dr Bridges1 and thank him for his interest in our recent publications.2, 3 In the course of his correspondence several incorrect statements were raised and, accordingly, we write to provide clarification.

The correspondent alludes to previous experimental studies (for example, those by Davidson et al.4) demonstrating gene transfer using open-chest cardiopulmonary bypass. Although demonstrating gene transfer to the large animal heart, the implications of these studies are very limited clinically, given that the majority of patients with advanced heart failure who may potentially benefit from gene delivery do not require cardiac surgery for other reasons such as coronary artery bypass grafting. Clearly, for patients with advanced heart failure, the risk of cardiopulmonary bypass and the attendant requirement for cardiac arrest and cardioplegic perfusion would be substantial, particularly as the potential benefit of gene delivery would not be realized immediately. Accordingly, following early pilot studies performed nearly a decade ago, we came to the conclusion that a cardiac surgical approach for recirculating gene delivery would have very little to offer in the routine care of patients with advanced heart failure. With this in mind, we developed a platform technology that could allow for the optimal delivery of gene therapy to the failing human heart using a nonsurgical physiological perfusion-based approach. As such, in our previous and more recent publication, we described the application of a novel percutaneous gene transfer system for the delivery of viral vectors encoding genes for well-validated targets in the failing heart. The technique described uses a recirculating principle based on the intracoronary delivery of a relevant agent with recollection from the coronary sinus, with subsequent oxygenation and reinfusion of the captured blood into the coronary artery.

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References

  1. Bridges CR . ‘Recirculating cardiac delivery’ method of gene delivery should be called ‘non-recirculating’ method. Gene Therapy 2009; 16: 939–940.

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  2. Kaye DM, Preovolos A, Marshall T, Byrne M, Hoshijima M, Hajjar R et al. Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J Am Coll Cardiol 2007; 50: 253–260.

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  3. Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM . Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Therapy 2008; 15: 1550–1557.

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  5. Penny DJ, Smolich JJ . Divergent effects of NO synthase inhibition on systemic and myocardial O2 delivery and consumption during dobutamine infusion in sheep. Pflugers Arch 2002; 443: 601–608.

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Authors and Affiliations

  1. Heart Failure Research Group, Baker Heart Research Institute, Melbourne, Victoria, Australia

    D M Kaye, M J Byrne & J M Power

Authors
  1. D M Kaye
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  2. M J Byrne
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  3. J M Power
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Correspondence to D M Kaye.

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Kaye, D., Byrne, M. & Power, J. Reply to Bridges. Gene Ther 17, 565–566 (2010). https://doi.org/10.1038/gt.2009.163

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