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Development of Novel Tau Retinal Tracers for Alzheimer's Disease and other Tauopathies

开发用于阿尔茨海默病和其他 Tau 病的新型 Tau 视网膜示踪剂

基本信息

批准号：
10323564
负责人：
Stella Sarraf
金额：
$ 49.22万
依托单位：
AMYDIS DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323564
关键词：
Address Affect Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease diagnostic Alzheimer&apos s disease therapeutic Alzheimer&apos s disease therapy Amyloid beta-Protein Animals Autopsy Binding Binding Proteins Biological Brain Characteristics Chemicals Clinical Trials Data Dementia Deposition Detection Development Diagnosis Diagnostic Diagnostic Imaging Diagnostic tests Disease Disease Progression Dose Early Diagnosis Eye Family Fluorescence Fluorescence Microscopy Fluorescent Probes Formulation Goals Health Expenditures Healthcare Systems Image Imaging Device Impaired cognition In Vitro Individual Injectable Lead Legal patent Libraries Microtubules Monitor Mus Neurobehavioral Manifestations Neurodegenerative Disorders Neurologist Outcome Pathology Patients Performance Pilot Projects Positron-Emission Tomography Process Property Protein Family Research Retina Secondary to Severity of illness Solubility Staging Symptoms Tauopathies Technology Testing Therapeutic Intervention Time Tissues Tracer Transgenic Mice Transgenic Organisms Visualization Work age related amyloid formation amyloid imaging base chemical stability clinical Diagnosis clinical diagnostics cognitive change cost experimental study in vivo innovation instrument lead candidate member mouse model novel novel diagnostics novel strategies protein misfolding prototype retinal imaging small molecule solid state tau Proteins tau aggregation tau conformation tau mutation

项目摘要

PROJECT SUMMARY Alzheimer’s disease (AD) is an age-related disease clinically diagnosed by the onset of dementia. This disease is defined by the formation of amyloid-beta (A) plaques and NFTs composed of tau aggregates. Although tau pathology has been considered secondary to A accumulation, it has been proposed that it may correlate more accurately to disease progression and cognitive changes. Abnormal tau aggregation occurs not only in the Alzheimer’s disease, but also in a family of protein-misfolding diseases called tauopathies. Currently, diagnosis of AD in individuals showing symptoms of cognitive decline is a lengthy and costly process, requiring multiple modes of testing over months to years. Early, pre-symptomatic diagnosis is even more challenging, if not impossible, with currently available technology. The only definitive way to diagnose AD is through post-mortem analysis. An ante-mortem diagnostic is needed that can reliably identify AD at the early, asymptomatic stages, enabling patients to get under the guidance of neurologist before the disease is at an advanced stage to maximize the opportunity for therapeutic intervention. Furthermore, a useful and affordable outcome marker is needed for clinical trials focused on therapies for AD/tauopathies that could stop or reverse progression of the disease. Amydis’ goal is to address these unmet needs by identifying tau in the eye, as a window to the brain, for early detection of AD/tauopathies. This proposal aims to develop small molecule fluorescent retinal tracers as a novel diagnostic for Alzheimer’s disease and tauopathies.

项目摘要阿尔茨海默病（AD）是一种年龄相关性疾病，临床上通过以下症状的发作来诊断：痴呆这种疾病的定义是淀粉样蛋白β（A β）斑块和NFT的形成由tau聚集体组成。尽管tau病理学被认为是继发于A β的，积累，有人提出，它可能更准确地与疾病进展和认知变化。异常tau聚集不仅发生在阿尔茨海默氏病，但也在一个家庭的蛋白质错误折叠疾病称为tau蛋白病。目前，在表现出认知下降症状的个体中诊断AD是一个漫长且复杂的过程。这是一个昂贵的过程，需要几个月到几年的多种测试模式。早期，症状前利用目前可用的技术，诊断甚至更具挑战性，如果不是不可能的话。诊断AD的唯一明确方法是通过尸检分析。一个死前的需要能够在早期无症状阶段可靠地识别AD的诊断，患者在疾病处于晚期之前接受神经科医生的指导，最大限度地增加治疗干预的机会。此外，一个有用的和负担得起的临床试验需要一个结果标志物，重点关注AD/tau蛋白病的治疗，阻止或逆转疾病的进展。Amydis的目标是通过以下方式解决这些未满足的需求鉴定眼睛中的tau，作为大脑的窗口，用于早期检测AD/tau蛋白病。这一项提案旨在开发小分子荧光视网膜示踪剂，作为一种新的诊断方法，阿尔茨海默病和tau蛋白病。