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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：
9980660
负责人：
GEOFFREY T MANLEY
金额：
$ 54.52万
依托单位：
UNIVERSITY OF FLORIDA
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 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9980660
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 Detection Development Diagnosis Diagnostic Disease Drug Evaluation Ethnic Origin Evaluation Research FDA approved Florida Future Gender Glasgow Coma Scale Glial Fibrillary Acidic Protein Gold Grouping Human Immunosorbents Injury Kinetics Knowledge Link Literature MAPT gene Measures Mild Concussions Military Personnel Nerve Degeneration Orthopedics Outcome Patient-Focused Outcomes Patients Performance Phase Plasma Post-Concussion Syndrome Prognostic Marker Proteins Reagent Recombinants Reference Values Risk Sampling Serum Severities Site Sports Standardization Testing Traumatic Brain Injury Validation Veterans Vision Work axon injury axonal degeneration base blood-based biomarker candidate marker cohort drug development member mild traumatic brain injury 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.

与神经学候选生物标志物分析验证的愿景一致疾病 PAR，我们组建了一个多学科团队，并提议对两种疾病进行分析验证新兴的 TBI 生物标志物：Tau 和磷酸化 Tau (P-Tau)。尽管最近 FDA 批准了一对标记物（神经元细胞体标记物 UCH-L1 和星形胶质细胞损伤标记物 GFAP）诊断颅脑 CT 异常然而，对于轻度 TBI 患者，迄今为止，还没有与轴突直接相关的合格且经过验证的生物标志物退行性轴突损伤和 TBI 后，特别是 TBU 后的急性和亚急性期。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 Tau/P-Tau 的两种使用情境 (COU) 作为复杂疾病的预后生物标志物轻度 TBI 患者有持续脑震荡后症状持续超过 3 个月的风险。而 Tau/P- Tau 是有前途的 TBI 预后生物标志物，但关于 Tau/P-Tau 存在显着的知识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 金标准品和汇总的阳性/阴性对照样本，用于 Tau/P-Tau 平台测试和标准化，(2) 评估新的 Tau/P-Tau 检测平台在两个分析条件下的分析性能 (3) 建立不同成人年龄的正常对照中 Tau 和 P-Tau 的基线血液水平间隔，（4）为急性/亚急性 Tau 和 P-Tau 水平作为血液生物标志物提供支持数据指定的 COU，(5) 建立不同严重程度的 TBI 患者血液 Tau、P-Tau 水平的时间分布和损伤类型，最后 (6) 制定 Tau/P-Tau TBI 生物标志物资格计划，提交给 FDA 生物标志物资格计划。