A blood test to predict sudden death risk

描述（由申请人提供）：ROS Technologies，Inc是一家医疗诊断公司，开发了一种血液检测，用于预测心力衰竭（HF）患者的猝死风险。心力衰竭影响着500多万美国人，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（SCN 5a）的状态。已知这些通道的调节会导致心律失常，例如当存在太少电流时的Brugada综合征和当存在太多电流时的长QT综合征。最近，我们报道了三种SCN 5a mRNA选择性剪接变体在人HF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，白色血细胞（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患者的心脏和血液中的全长Na+通道减少，变体增加。假说.由于SCN 5A是产生用于心肌中电传播的电流的主要通道，并且已知该通道中的突变会导致心肌猝死，因此我们假设Na+通道的这些截短的mRNA将有助于HF中的心肌猝死风险，并且通过量化它们在血液中的存在，将有可能开发有助于预测HF患者中猝死风险的血液测试。产品该I期申请将建立专有血液检测的可行性，以预测HF患者的AMI风险。如果成功，这种测试将是独一无二的，因为没有其他血液测试存在， 这个目的。具体目标1：确定WBC Na+通道mRNA变体丰度的改变是否与ICD患者的猝死风险可能性升高相关（通过适当出院测量）。第二阶段的计划。第二阶段将是对同一关系和产品原型开发进行前瞻性的多地点检查。商业应用。最初，罗斯新型血液检测将被医院（美国有5,000家）和医生用于每年超过50万名被诊断为HF的患者，以防止不必要的ICD植入。减少ICD的数量每年将为美国医疗保健系统节省约1.5亿美元。 公共卫生相关性：ROS Technologies，Inc.是一家医疗诊断公司，开发一种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是心脏性猝死的最高风险以及谁将从植入除颤器中受益。STTR的第一阶段应用旨在确定血液测试的可行性，以预测猝死风险，从而帮助将每年超过10亿美元的医疗费用用于最有可能受益的人。

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.