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MicroRNA Endotypes of Systemic Inflammation in Sub-Arachnoid hemorrhaGE (MESSAGE)

蛛网膜下腔出血全身炎症的 MicroRNA 内型 (MESSAGE)

基本信息

批准号：
9807502
负责人：
Sherry Hsiang-Yi Chou
金额：
$ 20.84万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2019-06-01 至 2021-08-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9807502
关键词：
Acute Affect Aneurysmal Subarachnoid Hemorrhages Autoimmune Diseases Biological Biological Markers Biological Process Blood Blood Banks Blood Circulation Blood specimen Brain Injuries Brain hemorrhage Case-Control Studies Cells Cerebral Aneurysm Cerebral Ischemia Characteristics Chemicals Clinical Clinical Trials Critical Care Data Destinations Development Disease Disease Progression Economic Burden Epidermal Growth Factor Receptor Functional disorder Future Gene Expression Heterogeneity Human Immune Immune response Inflammation Inflammatory Injury Intensive Care Units Interferon-beta Interleukin-6 Length of Stay Ligands Malignant Neoplasms Measurement Mediating Medicine MicroRNAs Molecular Target Morbidity - disease rate Multiple Sclerosis Organ Outcome Patient-Focused Outcomes Patients Phase Phenotype Plasma Population Prospective cohort Public Health Randomized Clinical Trials Rheumatoid Arthritis Risk Serum Societies Specific qualifier value Specificity Subarachnoid Hemorrhage Subgroup Survivors Systemic Inflammatory Response Syndrome TNF gene Testing Therapeutic Tissues Toll-like receptors Treatment Efficacy Up-Regulation Woman base biobank biomarker discovery biomarker validation candidate marker clinical care clinical development cohort cost cytokine design disability disease heterogeneity early detection biomarkers functional outcomes health economics immune function improved improved outcome macrophage malignant breast neoplasm microRNA biomarkers neuroinflammation new therapeutic target novel patient population patient subsets potential biomarker predictive modeling prospective recruit response therapeutic miRNA therapeutic target transcriptome validation studies

项目摘要

PROJECT SUMMARY Aneurysmal subarachnoid hemorrhage (SAH) is disproportionately lethal and morbid for young patients, causes extensive long-term disability, and results in significant health-economic burden to society. SAH is a heterogeneous condition. A unique feature of SAH is that, in addition to brain injury, patients can develop an acute and severe systemic illness with multiple extra-cerebral organ dysfunctions and a systemic inflammatory response syndrome. Several recent SAH clinical trials all failed to show therapeutic benefit partly due to the high degree of disease heterogeneity. A major barrier to a therapeutic breakthrough in SAH is the lack of appropriate biomarkers to identify patients most at risk for subsequent injury, complications, and bad outcome in this heterogenous population. Endotypes are biological subtypes defined by distinct pathophysiologic mechanisms that could be identified by corresponding biomarkers. Discovery of novel endotypes has led to major therapeutic breakthroughs in cancer and autoimmune diseases. MicroRNAs (miRs) are a novel class of molecules with ideal characteristics as potential biomarkers for systemic response to SAH because miRs are very stable in blood, very specific in their cells of origin and destination, can modulate biological processes in recipient cells by regulating gene expression, and are known to mediate inflammation and immune function. We have promising preliminary data showing that early increase in blood miR-26a after SAH is associated with favorable long-term outcome and possibly reduced risk for delayed cerebral ischemia (DCI), a major cause of morbidity. We hypothesize that blood miR-26a is an early biomarker for SAH long-term outcome and that miR-26a may modulate systemic inflammatory host response and reduce delayed cerebral ischemia (DCI). We propose to investigate miR-26a as a potential biomarker in an existing SAH patient cohort and biobank while simultaneously recruiting a separate, independent replication SAH cohort for prospective validation of this biomarker. As miRs may function in networks, we will explore the global blood miR transcriptome in a subset of patients to identify possible miR networks associated with SAH outcome and with DCI. To examine biological plausibility of miR- 26a in defining a novel inflammation endotype in SAH, we will explore the relationship between blood miR-26a expression and subsequent manifestations of clinical systemic inflammatory response syndrome and changes in blood inflammatory cytokine levels.

项目总结