Analytical validation of a multi‐protein, serum‐based assay for disease activity assessments in multiple sclerosis
Selected publication · PROTEOMICS – Clinical Applications, 2023
Qureshi F., Hu W., Loh L., Patel H., DeGuzman M., Becich M., Rubio da Costa F., Gehman V., Zhang F., Foley J., Chitnis T.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Patient Stratification Technical Evaluation | Serum |  Olink Focus |
Editor's note
Following a biomarker discovery investigation that employed multiple Olink Target 96 panels, scientists from Octave Bioscience developed a custom 21-protein PEA assay called the “Multiple Sclerosis Disease Activity” (MSDA) panel. This was developed with a view to improving the clinical management of MS patients using multiplexed serum protein analysis. In a critical step towards this aim, this article describes the successful “fit for purpose” technical validation of the MSDA panel. Subsequent articles also describe the clinical validation and practical application of the panel.
The authors concluded, “we demonstrated that a focused panel of MS biomarkers can be developed and optimized on the PEA platform with absolute quantitation of the proteins to support a fit-for-purpose analytical validation, thereby enabling clinical use of the assay”.
Abstract
Purpose
To characterize and analytically validate the MSDA Test, a multi‐protein, serum‐based biomarker assay developed using Olink® PEA methodology.
Experimental design
Two lots of the MSDA Test panel were manufactured and subjected to a comprehensive analytical characterization and validation protocol to detect biomarkers present in the serum of patients with multiple sclerosis (MS). Biomarker concentrations were incorporated into a final algorithm used for calculating four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score.
Results
Analytical characterization demonstrated that the multi‐protein panel satisfied the criteria necessary for a fit‐for‐purpose validation considering the assay’s intended clinical use. This panel met acceptability criteria for 18 biomarkers included in the final algorithm out of 21 biomarkers evaluated. VCAN was omitted based on factors outside of analytical validation; COL4A1 and GH were excluded based on imprecision and diurnal variability, respectively. Performance of the four Disease Pathway and overall Disease Activity scores met the established acceptability criteria.
Conclusions and clinical relevance
Analytical validation of this multi‐protein, serum‐based assay is the first step in establishing its potential utility as a quantitative, minimally invasive, and scalable biomarker panel to enhance the standard of care for patients with MS.