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，正在开发血液检查，以预测心力衰竭患者（HF）的猝死风险。心力衰竭会影响超过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，以帮助预测突然的死亡风险，这可能会阻止不必要的ICD植入物，并帮助筛查中度风险人群现在未接受治疗。该测试的一个优点是它反映了心脏NA+通道的状态（SCN5A）。这些通道的调节已知会引起心律不齐，例如当电流太少时，并且在存在太多电流时，QT综合征很少。最近，我们报道了三个SCN5A mRNA替代剪接变体在人HF组织中被上调。这些变体编码了非功能性心脏NA+通道。我们的初步数据表明，白细胞（WBC）具有异常的Na+通道mRNA剪接，WBC剪接与心脏中的剪接高度相关，并且与对照患者相比，HF患者的全长Na+通道降低了，心脏和血液中的变体增加。假设。由于SCN5a是心脏肌肉电气传播的主要渠道产生的电流，并且已知该通道中的突变会导致心律不齐的猝死，因此我们假设这些对Na+通道的截断的mRNA截断会导致HF的心律失常会导致血液中的心律失常，并且通过量化血液中的存在，可以量化其血液测试的患者，从而有助于患者突然死亡。产品。 I阶段的应用将确定专有血液测试的可行性，以预测HF患者的心律不齐风险。如果成功，该测试将是唯一的，因为没有其他血液检查 这个目的。具体目的1：确定WBC Na+通道mRNA变异的变化是否与ICDS患者适当出院衡量的突然死亡风险的可能性升高有关。第二阶段的计划。第二阶段将是对相同关系和产品原型开发的前瞻性多站点检查。商业应用。最初，ROS的新型血液检查将由医院（美国5,000名）和医生在每年被诊断出患有HF的50万名患者中使用，以防止不必要的ICD植入物。 ICD植入数量的减少将每年在美国医疗保健系统中节省约1.5亿美元。 公共卫生相关性：ROS Technologies，Inc。是一家医疗诊断公司，正在开发血液检查，以预测心力衰竭患者的猝死风险。每年有55万美国公民发生心力衰竭，但是没有简单，可靠的方法可以预测谁面临猝死的风险最高，谁会从植入的除颤器中受益。此I阶段的STTR应用程序旨在确定血液测试的可行性O预测猝死风险，从而帮助指导超过10亿美元的医疗费用，从而向最有可能受益的人指导。