Noninvasive biomarkers for gastrointestinal disease in preterm infants

早产儿胃肠道疾病的无创生物标志物

基本信息

批准号：
10493444
负责人：
Rebecca S Buckley
金额：
$ 105.67万
依托单位：
CHOSEN DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-24 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10493444
关键词：
Address Adopted Adoption Affect African American Air Alkaline Phosphatase American Antibiotic Therapy Biological Assay Biological Markers Birth Birth Weight Caring Cessation of life Characteristics Chronic Clinical Clinical Data Clinical Research Contracts Country Dependence Development Devices Diagnosis Diagnostic Disease Early Diagnosis Economics Emergency Situation Enrollment Equipment Evaluation Feces Feeds Freezing Future Gastroenterology Gastrointestinal Diseases Goals Growth Health Health Care Costs Healthcare Hospitals Human Image In Vitro Individual Infant Infection Inflammation Inflammatory Response Intestines Laboratories Length of Stay Life Link Logistics Louisiana Maiden Name Malnutrition Measurable Medical Metabolism Methods Microbe Minority Modeling Molecular Molecular Diagnosis Necrotizing Enterocolitis Neonatal Neonatology Nurses Operative Surgical Procedures Organ Pathology Patients Performance Phase Population Pregnancy Premature Birth Premature Infant Production Prospective Studies Protein phosphatase Publishing Quality of life Radiology Specialty Reagent Reference Values Reproducibility Research Resources Roentgen Rays Sampling Savings Scientist Sensitivity and Specificity Sepsis Severities Specificity Statistical Methods Stream Sum Survivors Symptoms Syndrome Technical Expertise Testing Time Translations Validation Very Low Birth Weight Infant X-Ray Medical Imaging accurate diagnosis accurate diagnostics biomarker identification burden of illness clinical diagnostics commercialization design diagnostic assay diagnostic tool disability disease diagnosis dysbiosis gastrointestinal gut homeostasis health disparity health inequalities imaging modality improved improved outcome infant death injured interest intestine surgery microbial mortality multidisciplinary neonatal patient neonate personalized medicine premature prevent prophylactic prototype response sample collection socioeconomics therapeutic development

项目摘要

PROJECT SUMMARY Our objective is to develop a clinically-usable test that can diagnose gastrointestinal disease early in infants. Initially described nearly 200 years ago, necrotizing enterocolitis (NEC) is the most frequent gastrointestinal disorder in preterm infants. It affects 7-12% of preterm infants born with very low birth weight (< 1.5 kg). Thus, nearly 6,000 preterm infants per year suffer from this bowel disease and an average total in-hospital treatment is $500,000 per infant. NEC is a lethal disease, due to delayed diagnosis: nearly 30% of infants who contract NEC die and median time to death is 1 day after x-ray imaging of free air in the intestine. Since NEC is not diagnosed with high specificity or in a timely fashion, survivors of surgical intervention are faced with long-term complications, such as shortened gut, nutritional deficiency, and neurodevelopmental delays. In sum, infants afflicted with NEC incur $5 billion in US medical care annually. Our value proposition is that early and accurate diagnosis would decrease the number of infant deaths, prevent long-term health challenges of survivors, and lower the economic expense of the disease. Such a model has three requirements to fulfill its commercialization promise. First, early detection of disease is actionable. Second, as prematurity is a health inequity, the method of testing is universally accessible regardless of resources, easy to adopt, and can integrate in current medical workflows. Third, disease delineation in patients, who are asymptomatic or present confounding general symptoms, opens new opportunities for therapeutic development and personalizing treatment for each patient. To achieve this, the initial barrier is elucidation of molecular characteristics, or biomarkers, that intersect with dysbiosis, human metabolism, and inflammatory responses of NEC. Our maiden biomarker, NECDetect, provides direct readout of an individual human’s ability to modulate gut homeostasis. For this application, we address unique technical, logistic, and regulatory challenges for NECDetect. To do so, we have assembled a multidisciplinary team of discovery scientists, clinicians, biomarker assay developers, and regulatory consultants. Project aims encompass kit prototype development, sample collection, assay validation, and sample analysis for regulatory evaluation. End goals are predictive disease segmentation of infants using the NECDetect prototype and reference values in the neonatal population.

项目摘要我们的目标是开发可诊断婴儿早期胃肠道疾病的临床检查测试。最初描述了大约200年前的坏死性小肠结肠炎（NEC）是最常见的胃肠道早产儿的障碍。它影响出生体重很低（<1.5 kg）的早产儿中7-12％。这是每年近6,000名早产儿，患有这种排便疾病和总院内平均治疗为每位婴儿$ 500,000。 NEC是一种致命的疾病，由于诊断的延迟：近30％的婴儿合同NEC死亡和死亡的中位时间是X射线成像在肠道中的X射线成像后的1天。自NEC以来没有被诊断出具有高特异性或及时的方式，外科干预的幸存者面临长期并发症，例如肠道缩短，营养缺乏和神经发育延迟。在总而言之，患有NEC的婴儿每年在美国医疗服务中产生50亿美元。我们的价值建议是准确的诊断将减少婴儿死亡人数，防止长期健康挑战幸存者，降低疾病的经济费用。这样的模型有三个要求来满足其商业化承诺。首先，早期发现疾病是可行的。第二，因为早产是健康不平等，无论资源如何，易于采用，都可以普遍访问测试方法，并且可以集成到当前的医疗工作流程中。第三，无症状或当前的混杂症状，为治疗性发育打开了新的机会为每个患者个性化治疗。为此，初始障碍是阐明分子与营养不良，人类代谢和炎症反应相交的特征或生物标志物 NEC。我们的处女生物标志物NecDect，可直接读取个人人类的能力调节肠道稳态。对于此应用，我们解决了独特的技术，逻辑和监管 Necdetect面临的挑战。为此，我们组建了一个跨学科科学家团队，临床医生，生物标志物测定开发人员和监管顾问。项目目标包括套件原型用于监管评估的开发，样品收集，测定验证和样本分析。最终目标是使用necdetect原型对婴儿进行的预测疾病分割，并在新生儿人口。