Placental Serum Amyloid A as a Therapeutic Target to Prevent Preterm Birth and Prematurity Related Morbidity
Document text
Principal Investigator: IRINA BURD Organization: UNIVERSITY OF MARYLAND BALTIMORE Fiscal Year: 2023 Award: $424,875 Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development 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. Terms: <0-11 years old><37 weeks completed gestation><37 weeks gestation><Acute><Age><Amyloid A Precursor><Amyloid A Protein-Related Serum Component><Amyloid Protein AA Precursor><Amyloid Protein SAA><Amyloid Serum Protein SAA><Amyloid-Related Serum Protein (SAA)><Animals><Beta Proprotein Interleukin 1><Binding><Biological Markers><Birth><Birth Rate><Blood Serum><Blood Vessels><Blood flow><Body Tissues><Brain><Brain Nervous System><Causality><Cell Death><Cells Placenta-Tissue><Cervix><Cervix Uteri><Child><Child Youth><Children (0-21)><Clinical><Data><Developed Countries><Development><Disease><Disorder><Dose><Encephalon><Etiology><Exposure to><Family><Fetal Tissues><Fluorescence><Genes><Genital Disorders><Goals><Harvest><Healthcare><IL-1 beta><IL-1 β><IL-1-b><IL-1β><IL1-Beta><IL1-β><IL1B Protein><IL1F2><IL1β><Immune><Immune response><Immunes><Immunological response><Industrialized Countries><Industrialized Nations><Infection><Inflammation><Inflammatory><Inflammatory Response><Infusion><Infusion procedures><Injury><Interleukin 1beta><Interleukin-1 beta><Interleukin-1β><Intravenous><Isoforms><Label><Link><Maternal-fetal medicine><Mediating><Mediator><Methodology><Molecular Interaction><Morbidity><Morbidity - disease rate><Mothers><Neurologic><Neurological><Normal Placentoma><Organ><Outcome><Parturition><Pathogenesis><Pathologic><Perinatal><Peripartum><Placenta><Placenta Embryonic Tissue><Placentome><Play><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Predisposition><Preinterleukin 1 Beta><Premature Birth><Premature Infant><Prematurely delivering><Preterm Birth><Preventative strategy><Prevention><Prevention strategy><Preventive strategy><Process><Protein Isoforms><Proteins><Publishing><Quelling><RNA Interference><RNA Interference Therapy><RNA Silencing><RNA based therapeutics><RNA based therapy><RNA interference therapeutics><RNA interference-based therapy><RNA therapy><RNAi><RNAi therapeutics><RNAi therapy><RNAi-based therapeutics><RNAi-based therapy><Receptor Protein><Recovery><Reporting><Reproductive System Disease><Research><Risk><Role><Route><Safety><Sequence-Specific Posttranscriptional Gene Silencing><Serum><Serum A Related Protein><Serum Amyloid A><Serum amyloid A protein><Short interfering RNA><Small Interfering RNA><Societies><Structure><Susceptibility><Technology><Therapeutic><Therapeutic Agents><Tissues><United States><Uterine Cervix><Uterus><Weaning><ages><behavior test><behavioral test><bio-markers><biologic marker><biomarker><care costs><causation><cytokine><developed country><developed nation><developed nations><developmental><disease causation><exposed in utero><fetal><fetal brain injury><fetal exposure><fetal loss><fetus loss><fetus tissue><health care><high reward><high risk><host response><imaging in vivo><immune system response><immunoresponse><in utero exposure><in vivo imaging><infants born premature><infants born prematurely><infusions><injuries><innovate><innovation><innovative><intra-uterine environmental exposure><intraperitoneal><intrauterine environmental exposure><kids><lipid based nanoparticle><lipid nanoparticle><mortality><mouse model><murine model><necrocytosis><neonate><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><novel><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><offspring><overexpress><overexpression><perinatal outcomes><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><placenta morphology><placental morphology><pre-clinical study><preclinical study><premature><premature baby><premature childbirth><premature delivery><premature infant human><prematurity><prenatal exposure><prenatally exposed><preterm baby><preterm delivery><preterm infant><preterm infant human><prevent><preventing><receptor><reproductive disease><reproductive disorder><reproductive system disorder><response><siRNA><side effect><site targeted delivery><social role><targeted delivery><therapeutic RNA><therapeutic target><vascular><womb><youngster>