Post-operative atrial fibrillation (post-op AF) is the most common compication of cardiac surgery. Post-op AF increases morbidity and mortality after surgery, including increased stay in the ICU and hospital, and increased risks of stroke, congestive heart failure and death. The impact on public health is substantial. Adding to the problems caused by post-op AF is the inadequacy of preventive therapies. We propose gene therapy as a new strategy to treat post-op AF. We have efficacy data in a pig model of post-op AF that shows prevention of sustained AF for 2 weeks after atrial gene transfer of AdKCNH2-G628S, a time that coincides with the window of risk for post-op AF. Here, we propose formal preclinical testing of AdKCNH2- G628S with the following specific aim: To successfully complete formal preclinical biodistribution and toxicology testing under Good Laboratory Practice (GLP)-certified conditions using Good Manufacturing Practice (GMP)-certified materials. Successful completion of this aim will complete the necessary preclinical testing before moving this idea to clinical trial.
Atrial fibrillation after cardiac surgery (post-op AF) is the most common complication of those procedures. Depending on the type of surgery; 20-70% of patients experience post-operative AF. These patients stay in the intensive care unit and in the hospital longer; they die sooner; and they have more strokes; heart attacks and respiratory failure than patients without AF. The impact on public health is equally substantial; with considerable expense related to the complications caused by post-op AF. Adding to the problems caused by AF is the lack of fully effective preventive therapies for this rhythm disorder. This proposal focuses on formal preclinical testing of a new therapy for post- op AF. We have preliminary data showing that gene therapy can eliminate AF. In this proposal; we will assess safety of this therapy before contemplating clinical trial.
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| Donahue, J Kevin (2016) Biological Therapies for Atrial Fibrillation: Ready for Prime Time? J Cardiovasc Pharmacol 67:19-25 |
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