Novel technologies for detection of podocytes from preeclamptic patients

检测先兆子痫患者足细胞的新技术

• 批准号: 9757792
• 负责人: Shrikumar Ambujakshan Nair
• 金额: $ 65.35万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-22 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757792
• 关键词: Accounting; Affect; Affinity; Antibodies; Binding; Blood; Blood Cells; Blood Pressure; Cell Line; Cells; Clinical; Collagen; Cost Savings; Crosslinker; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Equipment; Erythrocytes; Fetal Monitoring; Fetus; Funding; Glass; Hand; Healthcare Systems; Hospitalization; Hour; Human; Impairment; Kidney Failure; Lead; Life; Maternal Mortality; Measures; Methods; Monitor; Morbidity - disease rate; Mothers; Onset of illness; Patients; Peptides; Performance; Phase; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnant Women; Preparation; Process; Production; Proteinuria; Pulmonary Edema; Reproducibility; Reproducibility of Results; Research; Risk; Sampling; Second Pregnancy Trimester; Sedimentation process; Sensitivity and Specificity; Side; Slide; Specimen; Streptavidin; System; Technology; Testing; Thrombocytopenia; Time; United States; Urine; Urothelial Cell; Visual; body system; cell fixation; cell type; clinically significant; commercialization; cost; density; diagnostic biomarker; endothelial dysfunction; fetal; improved; liver function; manufacturing process; maternal morbidity; mortality; new technology; novel; patient population; podocyte; prototype; recruit; satisfaction; scale up

Preeclampsia is a complication of pregnancy characterized by elevated blood pressure, proteinuria, and endothelial dysfunction involving multiple organ systems. Worldwide, preeclampsia is the largest cause of fetal and maternal morbidity and mortality, and accounts for nearly 16% of maternal deaths in the United States alone each year. Currently, there is no approved diagnostic test to predict which patients will develop preeclampsia. Patients with preeclampsia require hospitalization and continuous monitoring of the mother and fetus, thus, there is an urgent and unmet need for a diagnostic test that can identify those patients at risk for preeclampsia. Preeclampsia is diagnosed when a patient’s blood pressure measures ≥140/90 mm Hg twice at least 4 hours apart and either proteinuria or one of the following conditions is present: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema or visual disturbances. Significant efforts are underway to detect preeclampsia prior to disease onset. Recently, it was demonstrated that glomerular podocytes are shed into the urine of preeclamptic patients and can be visualized using podocyte-specific antibodies. Moreover, shed podocytes can be detected in the second trimester, prior to preeclampsia diagnosis, with high sensitivity and specificity. Methods to detect podocytes currently rely on overnight culture and sedimentation of cells onto collagen-coated slides or Cytospin, which is prone to high false-positive rates due to contaminating red blood cells (RBCs) or casts. Inconsistencies in the method of podocyte detection and lengthy, overnight incubations susceptible to contamination weaken the utility of podocytes as a diagnostic marker of preeclampsia. We have identified proprietary peptides that bind with high affinity to podocytes but not to blood or urothelial cells, and we have developed a cell-specific coating for glass slides that provides a simple, reproducible method for preparing optimal capture slides from samples contaminated with blood and urothelial cells. A reduction in non-diagnostic results will improve the quality of podocyte capture and lead to significant cost savings by minimizing turnaround time and the need for expensive equipment. At the conclusion of this Phase II project, we will have sufficient data in hand to rapidly bring our peptide-conjugated slides to market.

先兆子痫是妊娠的并发症，其特征是血压升高，蛋白尿和 内皮族族族族族族式术戏剧化，全球范围内，先兆子痫是胎儿的最大原因 以及孕产妇的病人和死亡率，仅在美国，就占孕妇死亡的近16％ 每年。 先兆子痫的患者需要住院并防止母亲和胎儿监测 是诊断性测试的紧急且未满足的需求，可以识别那些有先兆子痫风险的患者。 当患者的血压测量≥140/90mm Hg至少两次4小时时，先兆子痫被诊断 除了蛋白尿或以下条件之一是：血小板减少症，肾脏不足， 肝功能受损，肺水肿或视觉障碍。 疾病发作之前的先兆子痫。 尿液可以使用特定于特异性的尿液进行预贴上专注的患者 在妊娠前诊断之前，可以检测到足细胞，具有高灵敏度，并且 特异性。 胶原蛋白涂层的载玻片或细胞蛋白，由于污染了红血体血液而容易产生高阳性率 细胞（RBC）或铸造的细胞不一致。 我们拥有的敏感型幼体作为诊断标记 鉴定出与足细胞亲和力结合但不与血液或尿路上皮细胞结合的专有肽，wee 已经开发了用于载玻片载玻片的细胞特异性涂层。 最佳的船长从被血液尿液细胞污染的样品中滑动。 结果将通过最小化周转来捕获足细胞的质量，并最大程度地节省成本 时间和昂贵的设备的需求。 手头的数据迅速将我们的肽偶联幻灯片推向市场。