课题基金 / 基金详情

Preclinical gene therapy development for post-operative atrial fibrillation

Preclinical gene therapy development for post-operative atrial fibrillation
术后房颤的临床前基因治疗开发
批准号:
8512334
负责人:
J Kevin Donahue
金额:
$31.6万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-03-15 至 2013-09-30

项目摘要

项目成果

J Kevin Donahue的其他基金

相似基金

相关文献

中文摘要
翻译
描述(申请人提供):术后房颤(POAF)是心脏手术后最常见的并发症。POAF增加了手术后的发病率和死亡率,增加了在ICU和医院的停留时间,并增加了中风、充血性心力衰竭、心肌梗死和死亡的风险。这对公众健康的影响是巨大的。特别是,POAF是老年人的问题,因为心脏手术的需要以及POAF的发病率、发病率和死亡率都随着年龄的增加而增加。目前可用的预防策略仍然允许POAF的发生率为30%。为了解决这一问题,我们提出了基因治疗作为预防POAF的新策略。我们有一个猪POAF模型的有效性和安全性数据显示,在AdKCNH2-G628S的心房基因涂抹后,持续两周的房颤预防,这一时间与POAF的风险窗口一致。绘制心房基因后,未见心律失常或其他不良反应。在这里,我们建议对AdKCNH2-G628S进行正式的临床前测试,具体目标如下:(1)成功完成定义最小有效剂量的剂量范围研究,以及(2)成功完成定义最大安全剂量的正式临床前生物分布和毒理学测试。成功完成这些目标将完成必要的临床前测试,然后将这种潜在的挽救生命的疗法投入临床试验。
英文摘要
DESCRIPTION (provided by applicant): Post-operative atrial fibrillation (POAF) is the most common complication following cardiac surgery. POAF increases morbidity and mortality after surgery, increases length of stay in the ICU and hospital, and increases risks of stroke, congestive heart failure, myocardial infarction and death. The impact on public health is substantial. In particular, POAF is a problem of the elderly, because the need for cardiac surgery, and the incidence, morbidity and mortality of POAF all increase as a function of age. Currently available preventative strategies still allow a 30% incidence of POAF. To combat this problem, we propose gene therapy as a new strategy to prevent POAF. We have efficacy and safety data in a pig model of POAF that shows prevention of sustained AF for 2 weeks after atrial gene painting of AdKCNH2-G628S, a time that coincides with the window of risk for POAF. We saw no proarrhythmia or other negative effects after atrial gene painting. Here, we propose formal preclinical testing of AdKCNH2-G628S with the following specific aims: (1) to successfully complete a dose-ranging study that defines minimum effective dose, and (2) to successfully complete a formal preclinical biodistribution and toxicology testing that defines maximum safe dose. Successful completion of these aims will complete the necessary preclinical testing before moving this potential life-saving therapy to clinical trial.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Translating post-infarct ventricular tachycardia mechanisms into a therapy
Calcium and MAPKinase Signaling and Structural Remodeling in Atrial Fibrillation
A phase I trial of AdKCNH2-G628S gene therapy for post-op atrial fibrillation
Calcium and MAPKinase Signaling and Structural Remodeling in Atrial Fibrillation
国内基金
海外基金
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
  • 依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
    雷芬芳
  • 依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    --
  • 批准年份:
    2024
  • 负责人:
    万荣
  • 依托单位: