I-Corps: Developing A Blood-Based Biomarker for the Detection and Monitoring of Amyotrophic Lateral Sclerosis

I-Corps：开发一种基于血液的生物标志物，用于检测和监测肌萎缩侧索硬化症

• 批准号: 2317745
• 负责人: Madhur Srivastava
• 金额: $ 5万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2317745&HistoricalAwards=false
• 关键词: Corps; Developing; Blood; Based; Biomarker

The broader impact/commercial potential of this I-Corps project is the development of a blood-based biomarker for the detection and monitoring of Amyotrophic Lateral Sclerosis (ALS). The advent of new drugs for treating ALS has resulted in increased demand for ALS detection. Currently, diagnosis times may take up to 2 years and cost about $40K per diagnostic test. The proposed technology may be used to develop a non-invasive, point-of-care diagnostic for ALS, that may be priced at $200 per test, which is comparable to a human immunodeficiency virus (HIV) diagnostic test. This may allow accessibility for the 80 million people in the at-risk population of the 50+ age-group as part of an annual health examine. Other potential applications of the proposed technology include vaccine quality assessment and detecting other neurological disorders.This I-Corps project is based on the development of a signal processing algorithm for utilizing Electron Spin Resonance (ESR) signals, a magnetic resonance spectroscopic technique, to detect the structural changes between two locations in proteins with biomarker precision. Determination of such structural changes using existing data analysis techniques from low-resolution ESR signals of blood samples containing the potential biomarker at critically low concentration is virtually impossible. The proposed data analytics is highly sensitive and selective in extracting the relevant structural parameters from data collected under these conditions. It has been confirmed that a protein, SOD1, in the blood is associated with ALS disease onset and progression. Specifically, the distance between the copper (Cu) centers in SOD1 increases from its standard value (healthy state) in the case of ALS patients. To measure the distance between two Cu centers in SOD1, the proposed algorithm carries out point-wise distance reconstruction, avoiding interference from neighboring points yielding local information in a precise manner. In proof-of-concept studies, structural changes were detected in SOD1 using the proposed data analytics at blood concentration levels. This technology may enable the development of a non-invasive and cost-effective diagnostic for ALS.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个I-Corps项目更广泛的影响/商业潜力是开发一种基于血液的生物标志物，用于检测和监测肌萎缩侧索硬化症（ALS）。 用于治疗ALS的新药的出现导致对ALS检测的需求增加。目前，诊断时间可能长达2年，每次诊断测试的成本约为4万美元。 所提出的技术可用于开发用于ALS的非侵入性护理点诊断，其可定价为每次测试200美元，这与人类免疫缺陷病毒（HIV）诊断测试相当。 这可能使50岁以上高危人群中的8 000万人能够获得作为年度健康检查的一部分。这项I-Corps项目的基础是开发一种信号处理算法，利用电子自旋共振（ESR）信号，一种磁共振光谱技术，以生物标志物的精度检测蛋白质两个位置之间的结构变化。使用现有的数据分析技术从含有极低浓度的潜在生物标志物的血液样品的低分辨率ESR信号确定这种结构变化几乎是不可能的。所提出的数据分析在从这些条件下收集的数据中提取相关结构参数方面具有高度敏感性和选择性。已经证实，血液中的一种蛋白质SOD 1与ALS疾病的发生和进展有关。具体而言，在ALS患者的情况下，SOD 1中的铜（Cu）中心之间的距离从其标准值（健康状态）增加。 为了测量SOD 1中两个Cu中心之间的距离，该算法进行逐点距离重建，避免相邻点的干扰，以精确的方式产生局部信息。在概念验证研究中，使用血液浓度水平的拟议数据分析检测到SOD 1的结构变化。这项技术可以使开发一种非侵入性和成本效益的诊断ALS.这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持.