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孕产妇和胎儿发病率和死亡率的重要原因。据认为，胎盘功能障碍是由异常滋养层分化和/或侵入引起的，这些事件发生在妊娠的前三个月， 但只有在妊娠中期和晚期才变得明显。胎盘功能障碍的最佳监测和管理，以及有效治疗的开发，由于缺乏早期和准确识别这种疾病风险的方法而受到阻碍。本项目旨在开发这样一种方法。目标1的目标是 从高危组群中鉴定用于预测临床相关胎盘功能障碍的候选细胞外RNA生物标志物。目标2将侧重于在平均风险队列中验证这些生物标志物。目标3将包括开发CLIA认证的检测方法，并将该方法应用于一项试点随机对照试验，以评估筛查一般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诊至更高水平的监测。该项目是学术界（UCSD）和工业界（Sera Prognostics）之间的合作，将利用现有和正在进行的资源，包括UCSD的胎盘功能障碍诊所，从Sera Prognostics的平均风险妊娠中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，包括母胎医学，临床研究，流行病学，基因组学，生物信息学，分子生物学和临床检测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胎盘功能障碍的风险， 我们的目标是将临床资源用于高风险病例，同时避免低风险患者不必要的焦虑。长期受益将来自于使用这种方法，通过靶向高风险患者来增加候选疗法临床试验的安全性和效力，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受到与该疗法相关的潜在风险的影响。

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.