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Analytical Validation of Tau and P-Tau as acute and subacute prognostic biomarkers for complicated mild TBI

Tau 和 P-Tau 作为复杂轻度 TBI 的急性和亚急性预后生物标志物的分析验证

基本信息

批准号：
10487403
负责人：
GEOFFREY T MANLEY
金额：
$ 51.09万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10487403
关键词：
Acute Adult Age Antibodies Antigens Archives Astrocytes Axon Biological Assay Biological Markers Blood Blood specimen Brain Concussion Cephalic Chronic Clinical Clinical Data Clinical Research Control Groups Data Development Diagnosis Diagnostic Disease Drug Evaluation Ethnic Origin FDA approved Fiber Optics Florida Future Gender Glasgow Coma Scale Glial Fibrillary Acidic Protein Gold Grouping Human Immunosorbents Injury Kinetics Knowledge Link Literature MAPT gene Measures Military Personnel Nerve Degeneration Orthopedics Outcome Patient-Focused Outcomes Patients Performance Phase Phosphorylation Plasma Post-Concussion Syndrome Prognostic Marker Proteins Qualifying Reagent Recombinants Reference Values Research Risk Sampling Serum Severities Site Sports Standardization TBI Patients Testing Traumatic Brain Injury UCHL1 gene Validation Vision Work axon injury axonal degeneration biological specimen archives biomarker validation blood-based biomarker candidate marker cohort detection assay detection platform detection sensitivity drug development member mild traumatic brain injury military veteran multidisciplinary nervous system disorder neurodevelopment neuronal cell body optical fiber pre-clinical research prognostic programs tau Proteins tau-1 tool development

项目摘要

Consistent with the vision of the Analytical Validation of a Candidate Biomarker for Neurological Disease PAR, we assembled a multidisciplinary team and propose to conduct analytical validation of two emerging TBI biomarkers: Tau and phospho-Tau (P-Tau). Although recently FDA approved a pair of markers (neuronal cell body marker UCH-L1 and astroglia injury marker GFAP) to diagnose cranial CT abnormality in mild TBI patients, however, to date, there are no qualified and validated biomarkers linked directly to axonal degenerative axonal injury and after TBI, especially in the acute and subacute phases after TBU. Emerging literature evidence and our own data point to blood-based Tau/P-Tau levels can fill these unmet biomarker needs. We propose two types of context of use (COU) for Tau/ P-Tau as prognostic biomarkers for complicated mild TBI patients at risk for persistent post-concussive symptoms lasting more than 3 months. While Tau/ P- Tau are promising TBI prognostic biomarkers, there are significant knowledge gaps regarding Tau/P-Tau biomarkers, as well as their detection assays. In this proposed study, we will (1) create Tau and P-Tau gold standards and pooled positive/negative controls samples for use in Tau/P-Tau platform testing and standardization, (2) assess the analytical performance of new assay platforms for Tau/P-Tau at two analytical sites, (3) establish the baseline blood levels of Tau and P-Tau in normative controls of different adult age intervals, (4) provide supportive data for acute/subacute Tau and P-Tau levels as blood-based biomarker for the indicated COU, (5) establish the temporal profile of blood Tau, P-Tau levels in TBI patients of varying severity and injury types, and lastly (6) assemble Tau/P-Tau TBI biomarker qualification plan for submission to FDA's Biomarker Qualification Program.

与神经病学候选生物标记物的分析验证的愿景一致疾病标准，我们组建了一个多学科团队，并建议对两个新出现的脑损伤生物标志物：Tau和磷酸Tau(P-Tau)。尽管最近FDA批准了一对标志物神经元体标记UCH-L1和星形胶质细胞损伤标记GFAP对颅脑CT异常的诊断价值然而，到目前为止，还没有与轴突直接相关的合格和有效的生物标志物。退行性轴索损伤和脑损伤后，尤其是脑损伤后的急性期和亚急性期。新兴文献证据和我们自己的数据表明，基于血液的Tau/P-Tau水平可以填补这些未满足的生物标志物需要。我们提出了两种Tau/P-Tau的使用环境(COU)作为复杂疾病的预后生物标志物轻度颅脑损伤患者有持续脑震荡后症状持续3个月以上的风险。而Tau/P- Tau是很有前景的脑损伤预后生物标志物，目前对Tau/P-Tau的认识还存在很大差距生物标志物及其检测分析。在这项拟议的研究中，我们将(1)创建Tau和P-Tau黄金用于Tau/P-Tau平台测试的标准和混合阳性/阴性对照样品标准化，(2)评估新的Tau/P-Tau分析平台的分析性能 (3)建立不同年龄段正常对照的Tau和P-Tau基线水平间隔，(4)提供急性/亚急性Tau和P-Tau水平的支持性数据，作为基于血液的生物标志物 (5)建立不同程度颅脑损伤患者血中Tau、P-Tau水平的时间分布和损伤类型，最后(6)编制Tau/P-Tau TBI生物标记物鉴定计划，提交给FDA 生物标记物资格认证计划。