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

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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.