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

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性侧索硬化症（ALS）。治疗肌萎缩侧索硬化症的新药的出现导致对肌萎缩侧索硬化症检测的需求增加。目前，诊断时间可能长达2年，每次诊断测试的费用约为4万美元。拟议的技术可用于开发ALS的非侵入性即时诊断，每次测试的价格可能为200美元，与人类免疫缺陷病毒（HIV）诊断测试相当。作为年度健康检查的一部分，这可能使50岁以上高危人群中的8000万人能够获得。拟议技术的其他潜在应用包括疫苗质量评估和检测其他神经系统疾病。I-Corps项目基于一种信号处理算法的开发，该算法利用电子自旋共振（ESR）信号，一种磁共振波谱技术，以生物标志物的精度检测蛋白质中两个位置之间的结构变化。利用现有的数据分析技术，从含有潜在生物标志物的低浓度血液样本的低分辨率ESR信号中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的敏感性和选择性。已经证实，血液中的蛋白质SOD1与ALS的发病和进展有关。具体而言，ALS患者SOD1中铜（Cu）中心之间的距离比标准值（健康状态）增加。为了测量SOD1中两个Cu中心之间的距离，提出的算法进行逐点距离重建，避免了邻近点的干扰，精确地产生了局部信息。在概念验证研究中，使用提出的血液浓度水平数据分析方法检测了SOD1的结构变化。这项技术可能使ALS的非侵入性和成本效益诊断的发展成为可能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.