Biomarker Panel for MS Relapse Diagnosis
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Solution Overview
Problem
Current biomarkers for multiple sclerosis (MS) relapses, such as serum neurofilament light chain (sNfL), lack specificity and sensitivity, making it difficult to distinguish between true relapses and pseudo-relapses, and to monitor treatment response effectively.
Innovation Solution
The use of a panel of biomarkers including urokinase plasminogen activator (uPA), kallikrein-8 (hK8), kallikrein-11 (hK11), and desmoglein-3 (DSG3), in combination with NfL, to diagnose relapses in MS patients by determining the level of expression in biological samples, thereby increasing sensitivity and specificity compared to using NfL alone.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If serum neurofilament light chain (sNfL) is used as a biomarker for MS relapses, then the detection of axonal damage is improved, but the specificity and sensitivity for distinguishing true relapses from pseudo-relapses deteriorates
Solution Approach 1:
The patent combines sNfL with three additional biomarkers (urokinase plasminogen activator, kallikrein-8, and desmoglein-3) into a multi-marker panel. This merging of multiple biomarkers compensates for the limitations of sNfL alone, providing both axonal damage detection and inflammatory activity assessment, thereby resolving the contradiction between detection capability and diagnostic reliability.
Solution Approach 2:
The multi-marker panel serves multiple functions simultaneously: it detects axonal damage (via sNfL), assesses inflammatory activity (via uPA, hK8, hK11, and DSG3), distinguishes true relapses from pseudo-relapses, and monitors treatment response. This multi-functionality resolves the limitation of sNfL which can only indicate axonal damage without providing specific relapse diagnosis.
2Ease of operation
If a single biomarker (sNfL) is used, then the simplicity of the test is maintained, but the ability to distinguish true relapses from pseudo-relapses and monitor treatment response deteriorates
Solution Approach 1:
The patent merges multiple biomarkers into a single integrated panel that can be assessed together through blood tests. While the number of markers increases, the methodology remains streamlined using blood-based assays, maintaining relative simplicity while dramatically improving diagnostic and monitoring capabilities compared to single-marker approaches.
3Ease of operation
If only sNfL is measured in blood, then the non-invasive nature of the test is maintained, but the sensitivity to detect minor disease-relevant fluctuations deteriorates
Solution Approach 1:
The patent combines multiple blood-based biomarkers (sNfL, uPA, hK8, hK11, DSG3) that respond to different aspects of disease pathology. This combination amplifies the detectable signal for disease activity, enabling blood tests to achieve sensitivity comparable to or exceeding CSF-based methods, while maintaining the non-invasive advantage of blood sampling.
Data Source
AI summary
The present invention includes a method of treating a subject having relapsing-remitting multiple sclerosis (RRMS) that is undergoing relapse, comprising: determining a level of expression for two or more biomarkers selected from urokinase plasminogen activator (uPA), kallikrein-8 (hK8), kallikrein-11 (hK11), or desmoglein-3 (DSG3) in a biological sample of a subject when compared to the same type of sample from a subject or a population of subjects that do not have RRMS; diagnosing that the subject in undergoing relapse if the level of expression of the two or more biomarkers has decreased in the subject; and administering a therapeutically effective amount of treatment for RRMS to the subject.