Refinement of a rapid saliva miRNA diagnostic test for concussion

脑震荡唾液 miRNA 快速诊断测试的改进

• 批准号: 10081522
• 负责人: David Levitskiy
• 金额: $ 38.08万
• 依托单位: QUADRANT BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081522
• 关键词: Acute; Address; Adolescent; Adolescent and Young Adult; Advanced Development; Age; Algorithms; Anxiety; Attention deficit hyperactivity disorder; Behavior; Behavioral; Biological; Biological Assay; Biological Markers; Biological Sciences; Biological Testing; Blood; Brain; Brain Concussion; Case-Control Studies; Characteristics; Child; Childhood; Chronic; Chronic Headaches; Clinical; Cognitive; Custom; Databases; Decision Making; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Emergency department visit; Employment; Exercise; Fatigue; Glial Fibrillary Acidic Protein; Headache; Image; Imaging technology; Individual; Injury; Machine Learning; Magnetic Resonance Imaging; Measurement; Measures; Medical; Mental Depression; Methods; MicroRNAs; Morbidity - disease rate; Neurologic; Olfactory Nerve; Oral cavity; Orthopedics; Participant; Patient Self-Report; Patient-Focused Outcomes; Patients; Pattern; Performance; Phase; Phenotype; Physical activity; Pilot Projects; Play; Population; Prospective Studies; Protein C; RNA Sequences; Reporting; Research; Risk; Risk-Taking; Saliva; Salivary; Sampling; School-Age Population; Schools; Severities; Social Interaction; Sports; Symptoms; Techniques; Test Result; Testing; Therapeutic Intervention; Time; Trauma; Venipunctures; accurate diagnosis; age group; aging population; base; blood-based biomarker; clinical care; concussive symptom; design; diagnostic panel; differential expression; improved; mechanical force; microRNA biomarkers; mild traumatic brain injury; minimally invasive; noninvasive diagnosis; novel; novel diagnostics; patient population; pediatric patients; peer; personalized management; potential biomarker; psychologic; tool; transcriptome sequencing; ubiquitin C-terminal hydrolase; young adult

Summary/Abstract - Quadrant Biosciences is developing a new diagnostic to aid in the clinical detection of mild traumatic brain injury (mTBI) in school-aged children and young adults (13–22 years). Based on salivary microRNA (miRNA) biomarkers, Quadrant’s diagnostic will provide an accurate, objective, and non-invasive method for mTBI diagnosis. Such a method is critically needed, as the number of pediatric mTBIs is on the rise, and the developing brains of young patients are more vulnerable to the after-effects of mechanical forces, leading to a wide range of negative effects on physical, cognitive, and psychological function. The diagnosis and assessment of mTBI in adolescents are challenging and rely on subjective measures, leading many mTBIs to go undiagnosed or underreported. This results in suboptimal post-injury treatment and patient management. A biologic assay to accurately diagnose adolescent mTBI would therefore provide an invaluable guide for clinical care, potentially guiding decisions for imaging, return to play, return to school, and therapeutic interventions. While a number of potential biomarkers for objectively detecting mTBI have been proposed, including the blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin c-terminal hydrolase (UCH-L1), recent research questions the ability of blood-based biomarkers to differentiate patients with mTBI from those with acute orthopedic trauma, particularly in pediatric populations. Moreover, these assays require venipuncture expertise that is not always available, particularly in the case of sports-related concussions, which account for nearly 1/3 of mTBIs in this patient population. To address these shortcomings, Quadrant Biosciences is creating a novel, objective diagnostic tool based on a panel of saliva miRNA biomarkers that are differentially expressed in patients with mTBI. Pilot studies in over 200 individuals with mTBI have identified a panel of saliva miRNAs capable of diagnosing mTBI and predicting symptom duration. In the proposed Fast Track project, Quadrant will advance development of this test by establishing a rapid, accurate method for quantifying these miRNAs and refining/validating a diagnostic algorithm to differentiate adolescents and young adults with mTBI from peers with symptomology that mimics mTBI (e.g. chronic headaches, anxiety/depression, ADHD, exercise-related fatigue, and orthopedic injury). In Phase I, Quadrant will refine a diagnostic algorithm for mTBI using a rapid quantification technique for saliva miRNAs. Machine learning will be used to develop a diagnostic algorithm that employs miRNA levels from the rapid multiplex assay alongside participant medical and demographic characteristics to predict mTBI status. In Phase II, Quadrant will validate the diagnostic algorithm for differentiating mTBI from medical conditions with overlapping symptomology in a prospective, case-control study of 2500 adolescents and young adults (age 13–22 years) to refine the saliva-based diagnostic aid for mTBI. Ultimately, Quadrant’s proposed salivary miRNA-based test will yield a minimally invasive, objective, biologic test that can aid diagnosis of mTBI, including among patients with confounding psychologic conditions.

摘要/摘要-跨骏生物科学公司正在开发一种新的诊断方法，以帮助临床检测轻度 学龄儿童和年轻人（13-22岁）的创伤性脑损伤（mTBI）。根据唾液 microRNA（miRNA）生物标志物，跨骏的诊断将提供一个准确，客观和非侵入性的 mTBI诊断方法。这种方法是迫切需要的，因为儿科mTBI的数量正在增加， 年轻患者的大脑发育更容易受到机械力的影响， 对身体、认知和心理功能产生广泛的负面影响。诊断和 青少年mTBI的评估具有挑战性，并且依赖于主观测量，导致许多mTBI 得不到诊断或被低估这导致了次优的损伤后治疗和患者管理。一 因此，准确诊断青少年mTBI的生物测定将为临床治疗提供宝贵的指导。 护理，可能指导成像，返回游戏，返回学校和治疗干预的决定。 虽然已经提出了许多用于客观检测mTBI的潜在生物标志物，包括血液 生物标志物胶质细胞酸性蛋白（GFAP）和泛素C末端水解酶（UCH-L1），最近的研究 质疑基于血液的生物标志物区分mTBI患者和急性TBI患者的能力。 骨科创伤，尤其是儿科人群。此外，这些测定需要静脉穿刺专业知识 这并不总是可用的，特别是在与运动有关的脑震荡的情况下，占近1/3 mTBI的比例。为了解决这些缺点，跨骏生物科学公司正在创造一种新的， 基于一组在患者中差异表达的唾液miRNA生物标志物的客观诊断工具 mTBI。在200多名mTBI患者中进行的初步研究已经确定了一组唾液miRNA， 诊断mTBI和预测症状持续时间。在拟议的快速通道项目中，跨骏将推进 通过建立快速、准确的方法来定量这些miRNA， 改进/验证诊断算法，以区分患有mTBI的青少年和年轻人与患有mTBI的同龄人。 模拟mTBI的神经病学（例如慢性头痛、焦虑/抑郁、ADHD、运动相关疲劳， 和骨科损伤）。在第一阶段，跨骏将使用快速定量技术改进mTBI的诊断算法， 唾液miRNAs技术。机器学习将用于开发诊断算法， 来自快速多重检测的miRNA水平以及参与者的医学和人口统计学特征， 预测mTBI状态。在第二阶段，Quadrant将验证用于区分mTBI和 在一项对2500名青少年进行的前瞻性病例对照研究中， 年轻人（年龄13-22岁），以完善基于唾液的mTBI诊断辅助。最终，Quadrant 一项基于唾液miRNA的检测将产生一种微创、客观的生物学检测，有助于诊断 mTBI，包括混杂心理状况的患者。