Part of Thermo Fisher Scientific

Improving MS clinical care with an innovative lab-developed test

Octave Bioscience’s 21-protein MS panel, leveraging PEA technology, offers a >90% accurate tool for monitoring MS, surpassing traditional biomarkers.

Illustration: Ibrahim Rayintakath

Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease of the central nervous system that exhibits a complex disease course and variable symptoms and manifestations. The heterogeneity in the clinical disease course of MS makes diagnosis and prognosis difficult, with no validated clinical tests to track disease activity or progression. To address this, Octave Bioscience (Menlo Park, CA) undertook a broad biomarker discovery approach to identify markers associated with clinical and radiographic endpoints in MS. The study included measurement of over 1,100 proteins using multiple Olink Target 96 panels and resulted in the identification of a 21-protein signature that could classify MS disease activity status with over 90% accuracy (area under the curve, AUC = 0.93).

This represented a substantial improvement compared to the established single biomarker, neurofilament light (NfL), which had an AUC of just 0.717. Moreover, the proteins in the model represented multiple pathways known to be significant in MS pathophysiology, emphasizing the biological relevance of the individual biomarkers.

Development and technical validation of a custom panel for MS disease activity monitoring

Building on the biomarker discovery study, the Octave team embarked on the development of a Laboratory Developed Test (LDT) with clinical utility, based on the 21 proteins identified. They designed a custom PEA panel developed at Olink, ensuring a smooth transition without the need to switch proteomics technologies.

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.
Qureshi et al., 2023

The Multiple Sclerosis Disease Activity (MSDA) panel underwent rigorous technical validation, with fifty-one plates processed using two different production lots over the course of a year. The evaluation criteria included accuracy, precision, sensitivity, assay interference, sample stability, and sample reanalysis across different equipment, reagents, location, and personnel. Of the 21 evaluated biomarkers, 18 met the acceptability criteria and were included in the final algorithm (APLP1, CCL20, CD6, CDCP1, CNTN2, CXCL13, CXCL9,FLRT2, GFAP, IL-12β, MOG, NfL, OPG, OPN, PRTG, SERPINA9, TNFRSF10A, and TNFSF13B). The assay accuracy was confirmed by mixing samples from four affected patients at different dilutions, and the percent recovery for each biomarker was determined to be within established limits. The expected Disease Activity Scores were calculated and compared to the observed scores, with a measured r² correlation of 0.997, well above the established acceptability criterion of >0.85.

Clinical validation of the MSDA panel

After the successful analytical validation of the panel, the crucial next phase was the clinical validation of the MSDA protein signature in extended cohort studies. As described in an article published in Clinical Immunology, the 18-protein MSDA test was validated based on associations between algorithm scores and clinical/ radiographic assessments using serum samples from 614 MS patients. The multi-protein model was trained based on presence/absence of gadoliniumpositive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease. The data obtained showed that the test was clinically validated, significantly outperforming the top-performing single-protein model and providing a quantitative tool to enhance the care of MS patients.

The MSDA Test is intended to complement standard radiographic imaging and clinical assessment and promote individualized disease management.
Qureshi et al., 2023

Real-world application of the MSDA panel

The full technical and clinical validation of the MSDA PEA panel opened up its practical application with multiple sclerosis patients. Dr. Taylor Gonyou, DO (Multiple Sclerosis Fellow, Michigan Institute for Neurologic Disorders) was the first physician to report on real-world testing in the clinic, as shown in the following video clip, recorded at the ACTRIMS Forum 2023 and showcased on NeurologyLive.

We’re using precision medicine for the first time in MS, and it’s a good way to find a baseline for patients.
Dr. Taylor Gonyou

Subsequent studies have further demonstrated the clinical utility of the panel. A team from the University of Pittsburgh extended the association of the protein biomarkers beyond purely physiological endpoints (lesion counts, brain atrophy etc.) and assessed protein levels in association with patient-reported disabilities. Taking data from two independent clinical cohorts, they applied machine learning to derive models to predict a Patient Determined Disease Steps (PDDS) score. A combined feature input of routine clinical factors and the panel proteins consistently outperformed base models in predicting severe versus mild/moderate PDDS disability across multiple ML approaches, with LASSO analysis achieving the best area under the curve with an impressive accuracy of AUC = 0.91. Interestingly, when NfL or GFAP (the currently used single protein biomarkers for MS) were used in combined models with the clinical features, they produced no improvement on the clinical features alone mode, emphasizing the power of multi-protein signatures compared to single biomarkers and illustrating how the initial broad biomarker discovery phase of the project enabled a more powerful and clinically useful panel to be developed.

The addition of serum biomarker profiles comprising multiple proteins primarily associated with MS inflammatory disease activity endpoints improved the model performance of machine learning approaches in predicting real-world disability status beyond clinical profile alone, reaching clinically actionable accuracy.
Zhou et al., 2023

A recent study undertaken by Octave Bioscience examined longitudinal changes in the selected proteins in relation to specific clinical (physical, cognitive, and radiographic) outcomes, with samples compared at baseline and at the end of the clinical follow-up period (average 5.4 years). This enabled the team to develop a series of both cross-sectional and longitudinal models for protein associations with multiple outcomes. Two observations of particular interest were that increased NfL was associated with greater cognitive decline and that the baseline levels of 7 proteins showed predictive associations with longitudinal outcomes – GFAP and PRTG showed particularly robust associations after multiple testing with brain imaging and cognitive score metrics.

Multi-protein assays may be essential in capturing the complex MS pathophysiology as part of the disease stratification, monitoring and potentially utilized as predictors of future accrual of pathology.
Jalaleddini et al., 2024

The findings were also of significant interest in terms of MS disease biology. The biomarkers comprising the MSDA panel cover 4 main disease pathway scores (immunomodulation, neuroinflammation, myelin biology, and neuroaxonal integrity) and the findings in this latest study indicated that the four MS pathways are differentially associated with distinct phenotypical and pathological changes. As the real-world use of this panel continues, the data suggests that its clinical utility may well be even more expansive than originally envisaged.

Related publications

Read publications related to the MSDA custom panel for multiple sclerosis

Accelerate your journey from discovery to clinical utility

PEA technology offers unparalleled precision in proteomics, simultaneously measuring thousands of proteins or specific biomarkers, bridging discovery to clinical application, and maximizing the impact of protein research on patient outcomes.

Olink Explore HT

Measure 5,400+ proteins with proven specificity to gain an understanding of disease at the protein level.


5,400+ With proven specificity


2 µL Plasma, serum & more

Olink Flex

Run individually tailored studies by combining up to 21 biomarkers from our extensive library with minimal sample volume.


~200 Pre-validated assays


1 µL Plasma, serum & more

Olink Target 96

Target specific disease areas or key biological processes with multiplex immunoassay panels.


1,100+ On 15 targeted panels


1 µL Plasma, serum & more

Olink Target 48

Extensively validated and carefully selected biomarkers for a comprehensive view of cytokine signaling and inflammatory processes.


89 On 2 panels


1 µL Plasma, serum & more