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Sigma-1 receptor activation on cardiac calcium channelopathy

Sigma-1 受体激活对心脏钙离子通道病的影响

基本信息

批准号：
9790930
负责人：
Jose Rafael Navarro Quejada
金额：
$ 4.06万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2020-06-26
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9790930
关键词：
Address Adult Agonist Arrhythmia Biomedical Engineering Birth Calcium Calcium Channel Cardiac Cardiac Myocytes Cell model Cells Clinical Coupling Cyclin-Dependent Kinase 5 Disease Disease model Drug usage Electrophysiology (science)Embryo Engineering FDA approved Fluvoxamine Functional disorder Gene Expression Goals Hand Heart Heart Diseases Heart failure Human Infant Inherited Knock-out Lead Long QT Syndrome Longevity Medical Mental Depression Mental disorders Modeling Molecular Mus Muscle Cells Neurons Outcome Patients Pharmaceutical Preparations Pharmacologic Substance Phenotype Play Proteins Reading Receptor Activation Regulation Rodent Model Role Selective Serotonin Reuptake Inhibitor System Testing Timothy syndrome Translating Ventricular Ventricular Tachycardia Wild Type Mouse drug candidate drug development drug testing experimental study gain of function mutation heart function in vivo Model induced pluripotent stem cell insight mouse model new technology new therapeutic target novel therapeutics overexpression sigma-1 receptor therapeutic target translational approach translational study voltage

项目摘要

Project Summary: Abnormal calcium handling such as calcium overload is associated with a variety of cardiac diseases including heart failure and arrhythmia. Our results from preliminary experiments using a pharmaceutical approach, showed that the sigma 1 receptor (Sigma-1R) is a new therapeutic target for the cardiac diseases associated with abnormal calcium handling. The goal of this study is to examine the effect of Sigma-1R activation on calcium handing, electrophysiological function, contraction and gene expression in genetically caused cardiac arrhythmia. We will use human induced pluripotent stem cell (iPSC) and rodent models to elucidate the molecular mechanism in which Sigma-1R restores cardiac function in inherited long QT syndrome. Preliminary results show that fluvoxamine, an FDA-approved drug, can be used as a Sigma-1R agonist for these diseases. Therefore, our translational study will provide new insight to inform the development of drugs for genetically caused cardiac diseases.

项目摘要：钙处理异常，如钙超载，与各种心脏疾病有关，包括心力衰竭和心律失常。我们的结果来自于使用药物方法的初步实验，显示sigma 1受体（Sigma-1 R）是心脏疾病相关的新治疗靶点，钙处理异常本研究的目的是检查Sigma-1 R激活对遗传性心脏病的钙操纵、电生理功能、收缩和基因表达心律不齐我们将使用人类诱导多能干细胞（iPSC）和啮齿动物模型来阐明 Sigma-1 R恢复遗传性长QT综合征心脏功能的分子机制初步结果表明，FDA批准的药物氟伏沙明可用作这些疾病的σ-1R激动剂。因此，我们的转化研究将为基因治疗药物的开发提供新的见解。导致心脏病。