Development of a novel fluorescent tracer for detection of retinal TDP43 in ALS and FTD

开发用于检测 ALS 和 FTD 中视网膜 TDP43 的新型荧光示踪剂

基本信息

批准号：
10483027
负责人：
Stella Sarraf
金额：
$ 45.85万
依托单位：
AMYDIS DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10483027
关键词：
ALS patients Alzheimer&apos s Disease Amyloid Amyloid beta-Protein Amyotrophic Lateral Sclerosis Anterior Binding Biological Markers Brain C-terminal Cadaver Cessation of life Characteristics Clinical Contrast Media Cytoplasmic Inclusion Data Degenerative Disorder Dementia Deposition Detection Development Diagnosis Diagnostic Diagnostic tests Disease Early Diagnosis Epitopes Event Exhibits Eye Fluorescence Frontotemporal Dementia Genotype Human Institution Intervention Label Lead Legal patent Light Lumbar spinal cord structure Measures Methods Mission Molecular Molecular Profiling Monitor Motor Cortex Motor Neuron Disease Nerve Degeneration Neurodegenerative Disorders Optical Coherence Tomography Paralysed Parkinson Disease Pathogenesis Pathology Patients Pattern Radial Research Retina Sampling Signal Transduction Spinal Spinal Cord Stains Structure Symptoms Technology Temporal Lobe Therapeutic Therapeutic Intervention Time Tissues Tracer Universities accurate diagnosis age related alpha synuclein beta pleated sheet cell type clinical candidate clinical development comorbidity frontotemporal lobar dementia-amyotrophic lateral sclerosis genetic risk factor genotyped patients high resolution imaging in vivo innovation misfolded protein molecular marker noninvasive diagnosis novel novel therapeutics prion-like protein TDP-43 research clinical testing retinal imaging small molecule tau mutation

项目摘要

Project Summary Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) define two ends of a spectrum of clinically, genetically, and mechanistically related neurodegenerative diseases. Due to symptom overlaps with other diseases, the early and accurate diagnosis of ALS and FTD is challenging. This leads to delayed intervention and stands as a major barrier to the efficient clinical testing of new disease-modifying therapeutics. Efforts to develop new therapies and apply them early would be greatly facilitated by biomarkers that reveal the state of ALS/FTD pathogenesis in vivo at the molecular level. Currently there are no objective diagnostics to non-invasively detect and measure the most defining molecular feature of ALS/FTD pathogenesis: accumulation of deposits of the TAR DNA-binding protein 43 (TDP43). A buildup of TDP43 deposits occurs in ~97% of ALS and ~50% of FTD cases and is thought to be a central driver of disease pathogenesis. This proposal will generate proof of concept for an affordable, accessible and innovative approach to detect and quantify TDP43 pathology in ALS/FTD human eyes using patent protected small molecule fluorescent retinal contrast agents.

项目概要肌萎缩侧索硬化症 (ALS) 和额颞叶痴呆 (FTD) 定义了谱系的两端临床、遗传和机械相关的神经退行性疾病。由于症状重叠与其他疾病相比，ALS 和 FTD 的早期准确诊断具有挑战性。这会导致延迟干预并成为有效临床测试新的疾病缓解疗法的主要障碍。揭示新疗法的生物标志物将极大地促进开发新疗法并尽早应用它们的努力分子水平上的 ALS/FTD 体内发病机制状态。目前尚无客观的诊断方法非侵入性检测和测量 ALS/FTD 发病机制最明确的分子特征：积累 TAR DNA 结合蛋白 43 (TDP43) 的沉积物。 TDP43 沉积物的积累发生在约 97% 的 ALS 中约 50% 的 FTD 病例，被认为是疾病发病机制的核心驱动因素。该提案将产生概念验证了一种经济实惠、易于使用且创新的方法来检测和量化 TDP43 病理学在 ALS/FTD 人眼中使用受专利保护的小分子荧光视网膜造影剂。