ExRNAs for Early Identification of Pregnancies at Risk for Placental Dysfunction

描述(由申请人提供)： 胎盘功能障碍，最常见的表现为先兆子痫或宫内生长受限，是发展中国家和发达国家母婴发病率和死亡率的重要原因。据认为，胎盘功能障碍是由于滋养层细胞分化和/或侵袭异常引起的，这些事件发生在怀孕早期， 但仅在妊娠中期和晚期临床表现明显。胎盘功能障碍的最佳监测和管理以及有效治疗方法的开发一直受到缺乏方法的阻碍，因为缺乏方法来早期和准确地识别有这种疾病风险的妊娠。本项目旨在开发这样一种方法。目标1的目标将是 从高危队列中确定预测临床相关胎盘功能障碍的候选细胞外RNA生物标记物。AIM 2将专注于在平均风险队列中验证这些生物标记物。目标3将包括开发CLIA认证的检测方法，并在试点随机对照试验中应用该检测方法，以评估筛查普通产科人群胎盘功能障碍风险的临床和成本影响，并将筛查阳性患者转至更高水平的监测。该项目是学术界(UCSD)和产业界(SERA Prognostics)之间的合作，将利用现有的和正在进行的资源，包括UCSD的胎盘功能障碍诊所、SERA Prognostics的中等风险妊娠收集的血浆和血清生物库，以及UCSD产科登记处。研究团队包括具有不同和互补优势的研究人员，包括母体胎儿医学、临床研究、流行病学、基因组学、生物信息学、分子生物学和临床化验开发方面的专业知识。立即应用一种简单而准确的方法来预测产科护理中临床相关的胎盘功能障碍的风险将 使临床资源能够针对高风险病例，同时避免低风险患者不必要的焦虑。通过针对高危患者，使用这种方法来提高候选疗法的临床试验的安全性和威力，从而增强对任何治疗效果的检测，并仅使最有可能受益的患者面临与该疗法相关的潜在风险，将产生更长期的好处。

DESCRIPTION (provided by applicant): Placental dysfunction, most commonly manifested as preeclampsia or intrauterine growth restriction, is an important cause of maternal and fetal morbidity and mortality in both the developing and developed world. It is thought that placental dysfunction arises from abnormal trophoblast differentiation and/or invasion, events that occur in the first trimester of pregnancy, but become clinically apparent only in the late second and third trimesters. Optimal surveillance and management of placental dysfunction, as well as the development of effective therapies, have been hampered by the lack of methods for early and accurate identification of pregnancies at risk for this disorder. This project aims to develop such a method. The goal of Aim 1 will be to identify candidate Extracellular RNA biomarkers for prediction of clinically relevant placental dysfunction from a high-risk cohort. Aim 2 will focus on validation of these biomarkers in an average-risk cohort. Aim 3 will include development of a CLIA certified assay and application of this assay in a pilot randomized control trial to assess the clinical and cost impact of screening general obstetric population for risk of placental dysfunction, and referral of screen-positive patients to a higher level of surveillance. This project is a collaboration between academia (UCSD) and industry (Sera Prognostics) and will leverage existing and in-progress resources, including the Placental Dysfunction Clinic at UCSD, the plasma and serum biobank collected from average-risk pregnancies at Sera Prognostics, and the UCSD Obstetric Registry. The research team includes investigators with diverse and complementary strengths, including expertise in maternal fetal medicine, clinical research, epidemiology, genomics, bioinformatics, molecular biology, and clinical assay development. The immediate application of a simple and accurate method to predict risk of clinically relevant placental dysfunction to obstetric care will be to enable targeting of clinical resources to high-risk cases, while sparing low risk patients unnecessary anxiety. Longer term benefits will arise from using this method to increase the safety and power of clinical trials of candidate therapies by targeting high-risk patients, thus enhancing the detection of any therapeutic effects and subjecting only the patients most likely to benefit to potential risks associated with the therapy.