Brain-enriched microRNAs detectable in plasma as biomarkers of Alzheimer's Disease

血浆中富含大脑的 microRNA 可作为阿尔茨海默病的生物标志物

基本信息

批准号：
10398256
负责人：
SAMUIL R UMANSKY
金额：
$ 62.48万
依托单位：
DIAMIR, LLC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10398256
关键词：
Affect Age Algorithms Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease care Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Alzheimer’s disease biomarker American Amyloid Biological Assay Biological Markers Biological Sciences Blood Brain Brain region Caring Characteristics Clinic Clinical Clinical Laboratory Improvement Amendments Clinical Protocols Clinical Research Clinical Trials Cognitive Collaborations Collection Computer software Data Data Analyses Dementia Detection Development Diagnostic Diagnostic tests Disease Documentation Double-Blind Method Elderly Enrollment Failure Family Functional disorder Geography Guidelines Heterogeneity Hippocampus (Brain)Individual Inflammation Institutes Internal-External Control Laboratories Long-Term Care Malignant Neoplasms Measurement Measures Medical Metabolic MicroRNAs Midbrain structure Monitor Nerve Degeneration Neurites Neurodegenerative Disorders Neurologist Participant Pathology Patients Pennsylvania Phase Plasma Preparation Procedures Process Prognosis Protocols documentation Quality Control Reaction Readiness Reagent Reproducibility Sampling Small Business Innovation Research Grant Specificity Specimen Synapses Technology Testing Universities Validation Vascular blood supply Washington Work base candidate marker circulating microRNA classifier algorithm clinical diagnosis cohort commercial application commercialization cross reactivity data analysis pipeline detection limit detection test diagnostic technologies diagnostic tool early screening human old age (65+)improved microRNA biomarkers mild cognitive impairment minimally invasive molecular diagnostics neuroimaging normal aging novel therapeutics patient screening payment performance tests phase 1 study phase 2 study pre-clinical programs research clinical testing screening sex validation studies

项目摘要

SUMMARY One in 10 Americans aged 65 and older have Alzheimer’s disease (AD). Since AD begins with a prolonged, over 10 year-long, asymptomatic stage, a growing number of companies are developing new therapies that aim to intervene early in the progression of AD and related forms of dementia. There is thus a great need for minimally invasive diagnostic tools for primary screening of individuals with early stages of the disease. DiamiR has developed a platform technology for detection, prognosis, and monitoring of different stages (from the preclinical stage to dementia) of AD based on targeted selection and analysis of brain-enriched and inflammation- associated microRNAs (miRNAs) circulating in blood plasma. Working with leading academic Alzheimer’s Disease Centers, DiamiR has produced a large amount of data, which supports the use of miRNA biomarkers for detection of AD at different stages of the disease. This data include detection of clinically diagnosed mild cognitive impairment (MCI) with accuracy of 95%, differentiation of AD from other neurodegenerative diseases with ≥80% accuracy, and identification of cognitively normal subjects who would later progress to MCI with 75% accuracy. Based on an analysis of over 1,000 well-characterized plasma samples, we defined 24 miRNAs for a diagnostic test, CogniMIRTM. The objective of the current Commercialization Readiness Program (CRP) is to develop a clinic-ready lab-developed test (LDT) compliant with Clinical Laboratory Improvement Amendments (CLIA) guidelines for detection of preclinical AD, MCI, and AD. In the ongoing Phase IIB study, we worked with the Roskamp Institute and Thermo Fisher Scientific to analyze multiple pre-analytical factors in order to minimize variability and increase sensitivity and reproducibility of the assay. We optimized the protocol for blood collection, plasma preparation, and miRNA extraction. Further, we have developed a detailed workflow for the analysis of 24-miRNA classifier. In the present CRP project, in partnership with Interpace Biosciences we will finalize assay protocol for the clinical setting and implement the test in a CLIA-compliant laboratory. Following analytical validation, we will perform a multi-center double-blinded cross-sectional clinical study to assess test performance for detection of preclinical AD, MCI, and AD among representative elderly subjects seen at geographically diverse Alzheimer’s Disease Centers in the US. Provided the project is successful, the new LDT comprising CogniMIRTM could be immediately used to help screen patients for MCI/AD clinical trials. Once the CogniMIRTM test is validated with 15,000-20,000 patient samples from heterogeneous cohorts, we will broadly launch the test to gerontologists/neurologists and other medical professionals engaged in AD treatment and care.

概括 65岁及以上的十分之一的美国人患有阿尔茨海默氏病（AD）。长达10年的无症状阶段，越来越多的公司正在开发新的疗法，旨在介入AD的早期和相关形式的痴呆症。侵入性的诊断工具，用于对疾病早期阶段的个体进行初级筛查。开发了一种平台技术，用于检测，预后和监测不同阶段痴呆症的阶段）AD以靶向选择和分析脑增强和发炎的分析 - 相关的microRNA（miRNA）在血浆中循环。疾病中心，Diamir产生了大量数据，该数据支持miRNA生物标志物的使用为了在疾病的不同阶段检测AD。认知障碍（MCI）精度为95％，AD与其他神经退行性疾病的区分 ≥80％的准确性，并确定认知正常受试者，后来将以75％的速度发展为MCI 准确性。诊断测试，cognimirtm。开发一个符合临床实验室改进的临床准备的实验室开发测试（LDT）（CLIA）在正在进行的IIB研究中检测临床前AD，MCI和AD的指南。 Roskamp Institute和Thermo Fisher Scientific分析了多个原始因素，以最大程度地减少可变性和增加关联的灵敏度和繁殖。血浆制备和miRNA提取。 24-miRNA分类器。临床环境和IMENT的方案在分析后实现了CLIA兼容的测试验证，我们将进行多中心的双盲横截面临床研究，以评估测试性能用于检测临床前AD，MCI和AD，在地理上看到的抑制性老年人中多元化的阿尔茨海默氏病在美国中心。 Cognimirtm可立即帮助筛查MCI/AD临床试验测试通过异质队列的15,000-20,000名患者样本验证向从事AD治疗和护理的其他医学专业人员和其他医学专业人员致敬。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Analytical Validation of a Novel MicroRNA Panel for Risk Stratification of Cognitive Impairment.

DOI：
10.3390/diagnostics13132170
发表时间：
2023-06-26
期刊：
DIAGNOSTICS
影响因子：
3.6
作者：
Kunwar, Arzu;Ablordeppey, Kenny Kwabena;Mireskandari, Alidad;Sheinerman, Kira;Kiefer, Michael;Umansky, Samuil;Kumar, Gyanendra
通讯作者：
Kumar, Gyanendra

Aging and aging-associated diseases: a microRNA-based endocrine regulation hypothesis.