Commercialization of a serum diagnostic for detection of Alzheimer's Disease

用于检测阿尔茨海默病的血清诊断剂的商业化

• 批准号: 9223628
• 负责人: Paul Andrew Hyslop
• 金额: $ 52.39万
• 依托单位: ARKLEY BIOTEK, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2018-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223628
• 关键词: Age; Aging; Alzheimer disease detection; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Antigens; Appearance; Autoantibodies; Autoantigens; Autoimmune Diseases; Benchmarking; Binding Sites; Biological Assay; Biological Markers; Blood; Blood Tests; Blood specimen; Brain; Brain imaging; Cerebrospinal Fluid; Chronic; Clinical; Clinical Trials; Cognitive; Collaborations; Data; Dementia; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Marker; Disease Progression; Early Diagnosis; Elderly; Enrollment; Enzyme-Linked Immunosorbent Assay; Ethnic Origin; Funding; Future; Gender; General Population; Goals; Guidelines; Heart Diseases; Huntington Disease; Imaging technology; Impaired cognition; Incidence; Indiana; Individual; Logistics; Longitudinal Studies; Malignant Neoplasms; Masks; Measurement; Measures; Medical; Memory; Neurodegenerative Disorders; Onset of illness; Outcome Study; Oxidation-Reduction; Phase; Phospholipids; Population; Prevalence; Process; Research; Research Design; Risk; Sampling; Serum; Small Business Innovation Research Grant; Specificity; Staging; Techniques; Technology; Test Result; Therapeutic Intervention; Time; United States National Institutes of Health; Universities; Validation; Vascular Dementia; Wasting Syndrome; age group; amnestic mild cognitive impairment; antigen binding; clinical research site; cognitive testing; commercialization; cost; design; effective therapy; falls; imaging biomarker; improved; in vitro testing; insight; neuroimaging; novel; potential biomarker; pre-clinical; product development; prognostic; public health relevance; screening; tool

 DESCRIPTION (provided by applicant): Commercialization of a blood diagnostic for early detection of Alzheimer's Disease The goal of this research is to demonstrate proof of concept in being able to utilize a disease marker in the blood to develop a diagnostic 'test' for the early detection and staging of Alzheimer's disease (AD). AD is a chronic neurodegenerative disease for which there is no cure. By 2050 the incidence of AD is expected to approach 1 million/year with a total estimated prevalence of 11-16 million at a cost of $172B. It is generally recognized that effective treatments for slowing or halting disease progression will have to be administered very early following onset of the disease. Identification of a robust blood test for identifying ealy AD will be essential as a population screening tool for identifying at-risk individuals for therapeutic interventions aimed at both halting disease progression and/or modifying the rate of cognitive decline. The sensitivity of cerebrospinal fluid biomarkers and brain imaging technologies to stage AD disease progression are improving, but fall short of being used as regular screening techniques for various reasons. At present there are no accepted biomarkers in blood that are clinically useful to identify individuals for developing AD. Recent discoveries have demonstrated that autoantibodies circulate in blood that have their antigen binding sites 'masked' such that they do not react with self-antigens. A novel class of masked autoantibodies against phospholipids (aPL) universally present in blood have been demonstrated to be present using proprietary technology to oxidatively 'unmask' autoantibody aPL reactivity. These redox-reactive autoantibodies (R-RAA) in blood samples can be quantitatively measured using standard clinical 'antigen down' ELISA assay formats, and form the basis of the diagnostic test. Studies have been completed that demonstrate that the level of R-RAA aPL are significantly elevated in blood samples from subjects with amnestic Mild Cognitively Impaired (MCI) compared to blood samples taken from cognitively normal age-matched healthy subjects. NIH SBIR funding will be used to enable testing of blood samples taken from a relatively large number of subjects over a period of time (longitudinal studies). The R-RAA aPL data from these studies will allow comparison of blood biomarker levels taken when subjects are asymptomatic and followed as the earliest signs of cognitive impairment become apparent. The studies will determine if the biomarker can be used for identifying at-risk asymptomatic individuals early in disease progression. A successful outcome of these studies will determine if clinical validation and commercialization of the R-RAA aPL diagnostic test is warranted for use as a screening tool to meet this very challenging unmet medical need.

 本研究的目的是证明能够利用血液中的疾病标志物来开发用于阿尔茨海默病（AD）的早期检测和分期的诊断“测试”的概念证明。AD是一种慢性神经退行性疾病，目前尚无治愈方法。到2050年，AD的发病率预计将接近100万/年，估计总患病率为1100 - 1600万，成本为1.72亿美元。人们普遍认为，减缓或阻止疾病进展的有效治疗必须在疾病发作后很早就给予。确定一个强大的血液测试，以确定早期AD将是必不可少的人口筛选工具，以确定有风险的个人，旨在阻止疾病进展和/或修改认知能力下降的速度的治疗干预。脑脊液生物标志物和脑成像技术对AD疾病进展分期的敏感性正在提高，但由于各种原因，不能作为常规筛查技术。目前，在血液中没有公认的生物标志物可用于临床识别个体是否发生AD。 最近的发现已经证明，自身抗体在血液中循环，其抗原结合位点被“掩蔽”，使得它们不与自身抗原反应。使用专有技术以氧化方式“暴露”自身抗体aPL反应性，已经证明存在一类新型的针对普遍存在于血液中的磷脂（aPL）的掩蔽自身抗体。血液样品中的这些氧化还原反应性自身抗体（R-RAA）可以使用标准临床“抗原下降”ELISA测定形式定量测量，并形成诊断测试的基础。 已经完成的研究表明，与取自认知正常的年龄匹配的健康受试者的血液样品相比，来自遗忘型轻度认知受损（MCI）受试者的血液样品中R-RAA aPL的水平显著升高。NIH SBIR资金将用于在一段时间内对相对大量受试者的血液样本进行检测（纵向研究）。这些研究的R-RAA aPL数据将允许比较受试者无症状时采集的血液生物标志物水平，并在认知障碍的最早体征变得明显时进行随访。这些研究将确定生物标志物是否可用于在疾病进展早期识别有风险的无症状个体。这些研究的成功结果将决定R-RAA aPL诊断测试的临床验证和商业化是否有必要用作筛查工具，以满足这一非常具有挑战性的未满足的医疗需求。