A blood test to predict sudden death risk

描述(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。心力衰竭影响了500多万美国人，增加了猝死的风险。这一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，并帮助筛查目前未接受治疗的中等风险人群。这项测试的一个优点是它反映了心脏Na+通道(SCN5A)的状态。已知这些通道的调制会导致心律失常，如电流太少时的Brugada综合征和电流太大时的长QT综合征。最近，我们报道了三种SCN5A mRNA选择性剪接变异体在人心力衰竭组织中上调。这些变体编码无功能的心脏Na+通道。我们的初步数据显示，与对照组相比，心力衰竭患者的白细胞(WBC)存在异常的Na+通道mRNA剪接，WBC剪接与心脏的剪接高度相关，心衰患者心脏和血液中的全长Na+通道减少，变异增加。假设。由于SCN5A是产生心肌电传播电流的主要通道，该通道的突变已知会导致心律失常性猝死，我们假设这些截短的Na+通道mRNAs将导致心力衰竭的心律失常风险，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力衰竭患者猝死风险的血液检测方法。产品。这一I期应用将确立专有血液测试的可行性，以预测心力衰竭患者的心律失常风险。如果成功，这项测试将是独一无二的，因为不存在其他血液测试 这就是目的。具体目标1：根据ICD患者适当的出院情况，确定WBC Na+通道mRNA变异丰度改变是否与猝死风险增加相关。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、多地点审查。商业应用。最初，ROS的新血液测试将被医院(美国有5000人)和医生寻求用于每年超过50万名被诊断为心力衰竭的患者，以防止不必要的ICD植入。ICD植入数量的减少将在美国医疗体系中每年节省约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55万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源性猝死的最高风险者，谁将从植入的除颤器中受益。这项第一阶段的STTR应用程序旨在建立血液测试的可行性，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直接分配给最有可能受益的人。

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.