A blood test to predict sudden death risk

预测猝死风险的血液测试

• 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
• 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

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，开发一种血液测试来预测心力衰竭（HF）患者的猝死风险。心脏衰竭影响了超过500万美国人，并增加了猝死的风险。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，从而防止不必要的ICD植入，并帮助筛选目前未接受治疗的中度风险人群。该测试的一个优点是它反映了心脏Na+通道（SCN5a）的状态。已知这些通道的调节可引起心律失常，如电流过低时的Brugada综合征和电流过大时的长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HF组织中上调。这些变异编码无功能的心脏Na+通道。我们的初步数据显示，白细胞（WBC） Na+通道mRNA剪接异常，WBC剪接与心脏剪接高度相关，与对照组相比，HF患者的心脏和血液中Na+通道全长减少，变异增加。假设。由于SCN5A是心肌电传播产生电流的主要通道，而已知该通道的突变会导致心律失常猝死，我们假设这些Na+通道的截断mrna会增加心衰患者的心律失常风险，通过量化它们在血液中的存在，将有可能开发一种有助于预测心衰患者猝死风险的血液测试。产品。这一I期应用将确立一种专有血液检测预测心衰患者心律失常风险的可行性。如果成功，这个测试将是独一无二的，因为没有其他血液测试存在