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Placental Serum Amyloid A as a Therapeutic Target to Prevent Preterm Birth and Prematurity Related Morbidity

胎盘血清淀粉样蛋白 A 作为预防早产和早产相关发病的治疗靶点

基本信息

批准号：
10742411
负责人：
IRINA BURD
金额：
$ 42.49万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10742411
关键词：
37 weeks gestation Acute Age Animals Binding Biological Markers Birth Birth Rate Blood Vessels Blood flow Brain Cell Death Cervix Uteri Child Clinical Data Developed Countries Development Disease Dose Etiology Exposure to Family Fetal Tissues Fluorescence Genes Goals Harvest Healthcare Immune Immune response Infection Inflammation Inflammatory Inflammatory Response Infusion procedures Injury Interleukin-1 beta Intravenous Label Link Maternal-fetal medicine Mediating Mediator Methodology Morbidity - disease rate Mothers Neurologic Organ Outcome Pathogenesis Pathologic Perinatal Placenta Play Predisposition Premature Birth Premature Infant Prevention Prevention strategy Process Protein Isoforms Proteins Publishing RNA Interference RNA Interference Therapy Recovery Reporting Research Risk Role Route Safety Serum Serum amyloid A protein Small Interfering RNA Societies Structure Technology Therapeutic Therapeutic Agents Tissues United States Uterus Weaning behavior test care costs cytokine fetal fetal brain injury fetal loss high reward high risk in vivo imaging innovation intraperitoneal lipid nanoparticle mortality mouse model neonate novel novel therapeutic intervention offspring overexpression perinatal outcomes personalized medicine placental morphology preclinical study premature prenatal exposure prevent receptor reproductive system disorder response side effect targeted delivery therapeutic RNA therapeutic target

项目摘要

Summary Preterm birth (PTB) and associated fetal brain injury bring about adverse perinatal outcomes including mortality in offspring, and high cost of care and treatment for the family and society. The pathologic immune responses in the placenta during maternal inflammation (MI) are thought to be the major causes of PTB and perinatal sequelae. Yet, the mechanisms are still not well understood because of the complexity of placental structure and function. Towards that end, there is a paucity of therapeutic agents capable of protecting offspring from exposure to MI. Serum amyloid A (SAA) has been identified as an inflammatory biomarker and its pathologic role has not been studied in the context of MI. Our published data demonstrated that one isoform, SAA2 was absent from the development in the placenta but highly susceptible to acute maternal inflammation. In this proposal, we plan to investigate the role of placental SAA isoforms in response to sub- chronic MI and explore whether inhibition of Saa2 systemically using small interfering RNA (siRNA) alleviates PTB and adverse offspring outcomes (Aim 1). Furthermore, we will compare the effect that whether administration of siRNA to Saa2 via targeted-placenta infusion will have higher efficacy and safety than via systemically infusion following sub-chronic maternal inflammation (Aim 2).The project will have a significant impact on the field of maternal-fetal medicine as it will provide placental SAA2 as a potential therapeutic target and will demonstrate a novel targeted-delivery route of siRNA to the placenta for the treatment of MI induced PTB and associated fetal brain injury.

总结