Commercialization of a Diagnostic Test for Alzheimer's Disease

阿尔茨海默病诊断测试的商业化

基本信息

批准号：
7997154
负责人：
MARK Anthony LOVELL
金额：
$ 43.57万
依托单位：
SCOUT DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-15 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7997154
关键词：
Affect Age Aging Aliquot Alzheimer&apos s Disease American Amyloid beta-Protein Antibodies Archives Basic Science Biological Biological Markers Brain Calibration California Cause of Death Cerebrospinal Fluid Collaborations Collection Complex Data Diagnosis Diagnostic Diagnostic tests Disease Disease Progression Enrollment Enzyme Immunoassay Enzymes Etiology Freezing Frontotemporal Dementia Funding Future Geographic Distribution Health Sciences Horseradish Peroxidase Housing Human Immunoassay Institution Instruction Label Laboratories Laboratory Study Letters Link Manuals Modification Molecular Weight Nerve Degeneration Oregon Oryctolagus cuniculus Paralysed Pathogenesis Patients Phase Population Heterogeneity Prealbumin Process Prostaglandin-Endoperoxide Synthase Prostaglandins Proteins Protocols documentation Recombinants Recruitment Activity Research Research Ethics Committees Sampling San Francisco Sensitivity and Specificity Serum Shipping Ships Site Small Business Technology Transfer Research Specificity Specimen Staging Statistical Data Interpretation Testing Therapeutic Intervention Threonine Time Training United States Universities Variant Washington Woman base blind commercialization corticobasal degeneration crosslink dimer innovation men mild neurocognitive impairment nervous system disorder novel prevent protein complex public health relevance research study tau Proteins tau-1 usability validation studies

项目摘要

DESCRIPTION (provided by applicant): The major barriers to preventing or treating Alzheimer's disease (AD) are its unknown pathogenesis/etiology and the lack of an objective, sensitive and specific biomarker of the disease, particularly at the early stages when therapeutic interventions would likely have the greatest efficacy. The basic hypothesis of this project is that levels of a unique high molecular weight protein/protein complex consisting of 1 molecule of lipocalin (brain-specific) prostaglandin-d-synthase (PDS) and 1 dimer of transthyretin (TTR) quantified in cerebrospinal fluid (CSF) using an enzyme linked immunoassay (ELISA) developed and characterized by Scout Diagnostics will serve as an effective biomarker to identify Alzheimer's disease (AD) subjects early in disease progression. To convert the basic science developed during Phase I funding to a commercially viable product, we propose to: a). synthesize and purify authentic PDS/TTR complex using recombinant human proteins generated in our laboratory for use as a standard for ELISA calibration and quantification; b) evaluate product storage and shipping requirements and prepare a horseradish peroxidase labeled probe antibody to decrease analysis time and; c) prepare and field test an instruction manual for use in independent diagnostic laboratories. To more fully characterize the PDS/TTR ELISA, we propose to analyze CSF specimens from an additional 150 AD and 150 control subjects from three geographically distinct Alzheimer's disease centers (ADCs) and to carry out inter-laboratory validation studies by providing those ADCs with ELISA kits, instructions and representative CSF specimens for analysis of duplicate aliquots of the same samples in their laboratories. In addition, we will further determine the specificity of the biomarker for AD patients by analyzing CSF from 50 subjects with non-AD neurologic disorders including frontotemporal dementia, corticobasal degeneration and parasupranuclear palsy. Overall, our preliminary data suggest that use of the PDS/TTR complex either in CSF or in serum may provide an objective biomarker with sufficient sensitivity/specificity for the identification of AD subjects. PUBLIC HEALTH RELEVANCE: Alzheimer's disease (AD) is the fourth leading cause of death in the United States and currently affects 4.5 million Americans. Two major barriers to treating and eventually preventing AD are: 1) the lack of understanding about the process of neuron degeneration and loss and 2) the lack of a sensitive and specific biomarker of the disease. Preliminary and future studies described in this proposal show that a novel protein-protein complex present in cerebrospinal fluid can be quantified using an enzyme linked immunoassay (ELISA). This protein-protein complex is a sensitive and specific biomarker of AD including early stages of AD (mild cognitive impairment) when therapeutic interventions are most likely to have beneficial effects.

描述（由申请人提供）：预防或治疗阿尔茨海默氏病（AD）的主要障碍是其未知的发病机理/病因，缺乏该疾病的客观，敏感和特定的生物标志物，尤其是在治疗干预措施可能具有最大功效的早期阶段。 The basic hypothesis of this project is that levels of a unique high molecular weight protein/protein complex consisting of 1 molecule of lipocalin (brain-specific) prostaglandin-d-synthase (PDS) and 1 dimer of transthyretin (TTR) quantified in cerebrospinal fluid (CSF) using an enzyme linked immunoassay (ELISA) developed and characterized by Scout Diagnostics will serve作为疾病进展早期鉴定阿尔茨海默氏病（AD）受试者的有效生物标志物。为了将I期资金中开发的基础科学转换为商业上可行的产品，我们建议：a）。使用在我们的实验室中产生的重组人蛋白作为ELISA校准和定量标准的重组人蛋白质合成和纯化真实的PDS/TTR复合物； b）评估产品存储和运输要求，并准备辣根过氧化物酶标记为探针抗体，以减少分析时间和； c）准备和现场测试指令手册以用于独立诊断实验室。为了更充分地表征PDS/TTR ELISA，我们建议分析来自AD的另外150个和150个对照对象，来自三个地理上不同的阿尔茨海默氏病中心（ADC）的CSF标本，并通过为ELISA KITS，指令和代表性csf的示例提供了这些ADC来进行分析，并通过为这些ADC提供这些ADC来进行分析，并通过为这些ADC提供这些ADC来进行分析。此外，我们将通过分析来自50名非AD神经系统疾病的患者的CSF进一步确定生物标志物对AD患者的特异性，包括额颞痴呆，皮质性龙皮质性变性和副班班纳核麻痹。总体而言，我们的初步数据表明，在CSF或血清中使用PDS/TTR复合物可以为鉴定AD受试者提供足够的敏感性/特异性提供客观的生物标志物。公共卫生相关性：阿尔茨海默氏病（AD）是美国第四大死亡原因，目前影响450万美国人。治疗和最终预防AD的两个主要障碍是：1）缺乏对神经元变性和损失过程的了解，以及2）缺乏疾病的敏感和特定的生物标志物。该提案中描述的初步研究表明，可以使用酶连接的免疫测定法（ELISA）来定量脑脊液中存在的新型蛋白质蛋白质复合物。这种蛋白质蛋白质复合物是AD的敏感且特异性的生物标志物，包括AD的早期阶段（轻度认知障碍），当时治疗干预措施最有可能具有有益的作用。