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

 描述(由申请人提供)：用于阿尔茨海默病早期检测的血液诊断的商业化这项研究的目标是证明能够利用血液中的疾病标记物来开发一种用于阿尔茨海默病(AD)早期检测和分期的诊断“测试”。AD是一种慢性神经退行性疾病，目前尚无治愈方法。到2050年，阿尔茨海默病的发病率预计将接近100万/年，总患病率估计为1100万至1600万，费用为1720亿美元。人们普遍认为，必须在疾病发作后很早就给予减缓或阻止疾病进展的有效治疗。作为一种人群筛查工具，确定用于识别阿尔茨海默病的可靠血液测试将是至关重要的，以识别高危个体，以进行旨在阻止疾病进展和/或改变认知功能减退率的治疗干预。脑脊液生物标志物和脑成像技术对AD疾病进展的敏感性正在提高，但由于各种原因，尚不能作为常规筛查技术使用。目前，血液中还没有公认的生物标志物可用于临床识别AD的个体。最近的发现表明，自身抗体在血液中循环，其抗原结合部位被屏蔽，因此不会与自身抗原发生反应。一类新的普遍存在于血液中的针对磷脂(APL)的掩蔽自身抗体已被证明存在，该抗体使用专利技术来氧化‘揭开’自身抗体APL的反应性。血液样本中的这些氧化还原反应性自身抗体(R-RAA)可以使用标准的临床‘抗原下降’酶联免疫吸附测定方法进行定量测定，并构成诊断试验的基础。已经完成的研究表明，与认知正常的年龄匹配的健康受试者相比，遗忘性轻度认知受损(MCI)患者的血液样本中R-RAA、APL水平显著升高。NIH SBIR资金将用于在一段时间内对相对较大数量的受试者进行血液样本检测(纵向研究)。来自这些研究的R-RAA APL数据将允许比较受试者无症状时的血液生物标记物水平，以及随着认知障碍的最早迹象变得明显时的血液生物标记物水平。这些研究将确定该生物标记物是否可以用于在疾病进展的早期识别高危无症状个体。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值得用作筛查工具，以满足这一非常具有挑战性的未得到满足的医疗需求。

 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.