GENE TRANSFER APPROACHES TO ATRIAL FIBRILATION

描述（由申请人提供）： 术后心房颤动（术后AF）是心脏手术最常见的并发症。术后AF增加了术后发病率和死亡率，包括ICU和医院住院时间增加，卒中、充血性心力衰竭和死亡风险增加。对公众健康的影响是巨大的。除了术后房颤引起的问题外，预防性治疗的不足也是一个问题。我们提出基因治疗作为治疗术后AF的新策略。我们在术后AF的猪模型中获得了有效性数据，该数据显示AdKCNH 2-G628 S在心房基因转移后可预防持续性AF 2周，这一时间与术后AF的风险窗口期一致。在此，我们提出AdKCNH 2-G628 S的正式临床前试验，具体目标如下：在药物非临床研究质量管理规范（GLP）认证的条件下，使用药物生产质量管理规范（GMP）认证的材料成功完成正式的临床前生物分布和毒理学试验。成功完成这一目标将完成必要的临床前测试，然后将这一想法转移到临床试验。

DESCRIPTION (provided by applicant): 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.