SBIR Phase I: Development and Validation of an In Vitro Diagnostic of HDL Cholesterol Efflux and Coronary Artery Disease Risk

SBIR 第一阶段：HDL 胆固醇流出和冠状动脉疾病风险体外诊断的开发和验证

• 批准号: 1248683
• 负责人: Joshua Schultz
• 金额: $ 15万
• 依托单位: Accent Assays, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248683&HistoricalAwards=false
• 关键词: SBIR; Phase; Development; Validation; Vitro

This Small Business Innovation Research (SBIR) Phase I project will develop a new approach to accurately predict coronary artery disease (CAD) risk. Because high-density-lipoprotein (HDL) protects from CAD, current methods to assess risk measure the cholesterol content of HDL (HDL-C) as a surrogate indicator of HDL quantity. However, the function of HDL, namely its ability to efflux cholesterol, is what reduces CAD risk. Obesity and diabetes predispose to CAD and compromise HDL cholesterol efflux activity. Because direct quantification of cholesterol efflux activity is not amenable to clinical laboratories, we developed a novel assay that uses electron paramagnetic resonance (EPR) spectroscopy to report indirectly on HDL?s cholesterol efflux activity. Our assay is performed in approximately 10 minutes on less than 10 µl of blood plasma/serum and is suitable for routine automated, high throughput clinical use. The objectives are: 1) validate the EPR assay compared to direct measurement of HDL cholesterol efflux activity, and 2) determine the predictive power of our assay to identify dysfunctional HDL in an established cohort of individuals with type 2 diabetes (METSIM). It is expected that this assay will have superior sensitivity and predictive power over all existing methods to determine CAD risk.The broader impact/commercial potential of this project is to enable rapid assessment of HDL function and accurately predict CAD risk, a multi-billion-dollar commercial opportunity in the medical diagnostics and drug development space. This project will develop and validate a rapid, sensitive and accurate assay that reports on HDL function. This innovative (first-in-class), discontinuous (goes beyond HDL-C), and transformational assay (highly specific measurement of HDL function directly in plasma) can be used as a diagnostic assay to identify patients at risk, even those with normal HDL-C levels, and as a surrogate outcome measure in clinical trials and patient management. The exceptional capability of our assay to serve as a window on metabolic disease status in an age- and gender-independent fashion is unprecedented. This technology promises to greatly improve the early diagnosis of CAD and metabolic disease predisposition and facilitate the discovery and implementation of interventions to prevent disease and significantly reduce long-term healthcare costs. The still broader use of EPR spectroscopy to measure structural changes in proteins as functional biomarkers of disease represents a platform innovation that denotes a new era of sophistication for molecular diagnostics.

该小型企业创新研究 (SBIR) 第一阶段项目将开发一种新方法来准确预测冠状动脉疾病 (CAD) 风险，因为高密度脂蛋白 (HDL) 可以预防 CAD，目前评估风险的方法是测量冠状动脉疾病 (CAD) 的胆固醇含量。 HDL (HDL-C) 作为 HDL 数量的替代指标 然而，HDL 的功能（即其排出胆固醇的能力）可降低 CAD 风险，并降低 HDL 的风险。由于临床实验室无法直接定量胆固醇流出活性，因此我们开发了一种新的检测方法，使用电子顺磁共振 (EPR) 光谱来间接报告 HDL 的胆固醇流出活性。我们的检测大约在 10 小时内进行。分钟内即可检测不到 10 µl 血浆/血清，适合常规自动化、高通量临床使用。目标是：1) 与直接测量相比验证 EPR 测定。 HDL 胆固醇流出活性，以及​​ 2) 确定我们的检测方法的预测能力，以识别已建立的 2 型糖尿病患者队列 (METSIM) 中识别 HDL 的功能障碍。预计该检测方法将比所有现有的检测方法具有更高的灵敏度和预测能力。该项目更广泛的影响/商业潜力是能够快速评估 HDL 功能并准确预测 CAD 风险，这是医疗诊断和药物开发领域的数十亿美元的商业机会。并验证一种快速、灵敏且准确的报告 HDL 功能的检测方法，这种创新的（一流的）、不连续的（超越 HDL-C）和转化检测方法（直接在血浆中高度特异性地测量 HDL 功能）可用作一种诊断检测，可识别处于危险中的患者，甚至是那些 HDL-C 水平正常的患者，并作为临床试验和患者管理中的替代结果衡量指标。并且不分性别这项技术有望大大改善 CAD 和代谢疾病易感性的早期诊断，促进预防疾病的干预措施的发现和实施，并显着降低长期医疗成本。蛋白质作为疾病的功能性生物标志物代表了一种平台创新，标志着分子诊断复杂化的新时代。