A blood test to predict sudden death risk

预测猝死风险的血液测试

基本信息

批准号：
8392935
负责人：
SAMUEL C DUDLEY
金额：
$ 26.98万
依托单位：
ROS TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-20 至 2015-07-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8392935
关键词：
A Mouse Affect Alternative Splicing American Anti-Arrhythmia Agents Arrhythmia Blood Blood Tests Cardiac Cardiac Surgery procedures Cessation of life Chronic Clinical Trials Communities Data Defibrillators Development Devices Diagnosis Diagnostic EFRAC Emergency Situation Foundations Gold Healthcare Systems Heart Heart Diseases Heart failure Hemorrhage Hospitals Human Implant Laboratories Left Ventricular Ejection Fraction Length Leukocytes Life Long QT Syndrome Manuscripts Marketing Measures Mediation Medical Messenger RNA Mutation Myocardial Infarction Myocardium Operative Surgical Procedures Patient Selection Patients Perforation Phase Physicians Pneumothorax Population Process RNA Splicing Reporting Risk Screening procedure Small Business Technology Transfer Research Stratification Stroke Sudden Death Syndrome Techniques Technology Testing Time Tissues Variant base clinical application commercial application cost effective experience high risk implantable device implantation mouse model novel prevent product development prospective prototype sudden cardiac death

项目摘要

DESCRIPTION (provided by applicant): ROS Technologies, Inc, is a medical diagnostics company developing a blood test to predict sudden death risk in patients with heart failure (HF). Heart failure affects more than five million Americans and increases the risk of sudden death. This application sets out to develop a simple, inexpensive blood test to help predict sudden death risk that may prevent unnecessary ICD implants and help screen moderate risk populations now not treated. One advantage of this test is that it reflects the state of cardiac Na+ channels (SCN5a). Modulation of these channels is already known to cause arrhythmias such as Brugada Syndrome when too little current is present and Long QT syndrome when too much current is present. Recently, we reported three SCN5a mRNA alternative splicing variants are upregulated in human HF tissue. These variants encoded nonfunctional cardiac Na+ channels. Our preliminary data show that white blood cells (WBCs) have abnormal Na+ channel mRNA splicing, that WBC splicing is highly correlated with that in heart, and that HF patients have reduced full length Na+ channel and increased variants in their heart and blood when compared to control patients. Hypothesis. Since SCN5A is the main channel generating current for electrical propagation in heart muscle and mutations in this channel are known to cause arrhythmic sudden death, we hypothesize that these truncated mRNAs for the Na+ channel will contribute to arrhythmic risk in HF, and by quantifying their presence in blood, it will be possibl to develop a blood test that would help predict sudden death risk in HF patients. Product. This phase I application will establish the feasibility of a proprietary blood test to predict arrhythmi risk in HF patients. If successful, this test would be unique, since no other blood tests exist for this purpose. Specific aim 1: To determine if altered WBC Na+ channel mRNA variant abundances are associated with an elevated likelihood of sudden death risk as measured by appropriate discharge in patients with ICDs. Plans for Phase II. Phase II would be a prospective, multisite examination of the same relationship and product prototype development. Commercial Application. Initially, ROS' novel blood test will be sought by hospitals (5,000 in the US) and physicians for use in over 500,000 patients who are diagnosed with HF annually in order to prevent unnecessary ICD implants. A reduction in the number of ICD implantations would save ~$150 million annually in the US healthcare system. PUBLIC HEALTH RELEVANCE: ROS Technologies, Inc. is a medical diagnostics company developing a blood test to predict sudden death risk in patients with heart failure. Heart failure occurs in more than 550,000 US citizens each year, but there are no simple, reliable ways of predicting who is at highest risk for sudden cardiac death and who will benefit from an implanted defibrillator. This Phase I STTR application sets out to establish the feasibility of a blood test o predict sudden death risk and thereby help direct more than $1 billion/year in medical expenses to those most likely to benefit.

描述（由申请人提供）：ROS Technologies, Inc 是一家医疗诊断公司，开发血液测试来预测心力衰竭 (HF) 患者的猝死风险。心力衰竭影响超过五百万美国人，并增加猝死的风险。该应用程序旨在开发一种简单、廉价的血液测试，以帮助预测猝死风险，从而可以防止不必要的 ICD 植入，并帮助筛查目前未接受治疗的中度风险人群。该测试的优点之一是它反映了心脏 Na+ 通道 (SCN5a) 的状态。已知这些通道的调节会导致心律失常，例如电流过少时的布鲁格达综合征和电流过多时的长 QT 综合征。最近，我们报道了三种 SCN5a mRNA 选择性剪接变体在人类心力衰竭组织中上调。这些变体编码非功能性心脏 Na+ 通道。我们的初步数据显示，白细胞（WBC）存在异常的Na+通道mRNA剪接，并且WBC剪接与心脏中的剪接高度相关，并且与心力衰竭患者相比，心力衰竭患者的心脏和血液中全长Na+通道减少，变异增加控制患者。假设。由于 SCN5A 是产生心肌电传播电流的主要通道，并且已知该通道的突变会导致心律失常性猝死，因此我们假设这些 Na+ 通道截短的 mRNA 将导致心力衰竭的心律失常风险，并通过量化它们的存在在血液中，将有可能开发出一种有助于预测心力衰竭患者猝死风险的血液测试。产品。这一第一阶段的应用将确立专有血液测试预测心力衰竭患者心律失常风险的可行性。如果成功，该测试将是独一无二的，因为不存在其他血液测试这个目的。具体目标 1：确定 WBC Na+ 通道 mRNA 变异丰度的改变是否与猝死风险升高的可能性相关（通过 ICD 患者的适当出院来衡量）。第二阶段计划。第二阶段将是对相同关系和产品原型开发的前瞻性、多地点检查。商业应用。最初，ROS 的新型血液检测将被医院（美国有 5,000 家）和医生寻求用于每年超过 500,000 名被诊断为心力衰竭的患者，以防止不必要的 ICD 植入。减少 ICD 植入数量每年将为美国医疗保健系统节省约 1.5 亿美元。公共健康相关性：ROS Technologies, Inc. 是一家医疗诊断公司，开发血液测试来预测心力衰竭患者的猝死风险。每年有超过 550,000 名美国公民发生心力衰竭，但没有简单、可靠的方法来预测谁最有可能发生心源性猝死，以及谁将受益于植入式除颤器。这一第一阶段的 STTR 申请旨在建立血液测试预测猝死风险的可行性，从而帮助将每年超过 10 亿美元的医疗费用转移给最有可能受益的人。