How AI and Blood Biomarkers Transform the Monitoring of Multiple Sclerosis: The MSDA Test

For many years, scientists have known that the blood of patients with multiple sclerosis (MS) contains dozens of biologically meaningful proteins—biomarkers that reflect inflammation, myelin damage, axonal injury, astrocyte activation, and the integrity of the blood–brain barrier (BBB).

However, for decades it was nearly impossible to use these biomarkers in real-world clinical practice. The reasons were clear:

• each biomarker reflects only one specific process,
• values vary greatly from person to person and over time,
• no single biomarker can describe the full complexity of MS,
• and clinicians had no tools capable of interpreting many biomarkers simultaneously.

Researchers long suspected that the real value would come from analyzing multiple biomarkers together, forming a biological “fingerprint” of disease activity. But such analysis became possible only with the arrival of high-precision proteomics, large datasets, and modern artificial intelligence.

The Multiple Sclerosis Disease Activity (MSDA) Test, developed by Octave Bioscience (USA), is one of the first clinically validated MS tools based on this approach. By analyzing 18 biomarkers in the blood and processing them with advanced AI algorithms, the MSDA Test produces a quantitative score that reflects the underlying biological activity of MS — even when MRI or symptoms appear stable.

What Is the MSDA Test?

The MSDA Test is a serum-based, multi-protein assay that measures 18 biomarkers related to the key mechanisms of MS:

• immune activation,
• neuroinflammation,
• myelin damage and repair,
• axonal injury and neurodegeneration,
• astrocyte reactivity,
• blood–brain barrier dysfunction.

These biomarkers are not interpreted individually. Instead, their combined profile is analyzed by a proprietary AI-based algorithm that generates:

• a Disease Activity Score (low, moderate, or high),
• four Pathway Scores, reflecting:
  • Immunomodulation
  • Neuroinflammation
  • Myelin Biology
  • Neuroaxonal Integrity

MSDA does not replace MRI or neurological evaluation, but it adds an important biological dimension that helps understand how active the disease truly is at a given moment.

How the MSDA Algorithm Works: 18 Proteins + AI

The MSDA Test uses the highly sensitive Proximity Extension Assay (PEA) platform, which allows accurate measurement of many proteins simultaneously in a small serum sample.

The process includes:

• Blood draw in serum tubes.
• Measurement of 18 biomarkers using the PEA platform in a CLIA-certified, CAP-accredited laboratory.
• Data normalization by age, sex, and analytical standards.
• AI-based modeling, where a stacked classifier analyzes the biomarker patterns.
• Calculation of:
  • a Disease Activity Score (1.0–10.0),
  • four pathway scores.

The power of the MSDA Test lies not in any single biomarker but in the multidimensional pattern captured by the algorithm — something that cannot be replicated by simple arithmetic or single-marker measurements.

What the 18 Biomarkers Represent

Below is a patient-friendly summary of the biological meaning of each biomarker included in the MSDA panel.

Markers of immune activity and inflammation

• CCL20 — attracts immune cells involved in inflammatory responses.
• CXCL9, CXCL13 — chemokines regulating T- and B-cell migration; associated with CNS inflammation.
• IL-12β — key cytokine subunit supporting Th1/Th17 immune pathways.
• TNFSF13B (BAFF) — crucial for B-cell survival and activation.
• TNFRSF10A (TRAIL-R1) — regulates cell death and immune balance.
• CD6 — marker of T-cell activation and adhesion.
• CDCP1 — involved in cell migration and vascular inflammatory changes.
• OPN (osteopontin) — inflammatory mediator associated with MS relapses and severity.
• OPG (osteoprotegerin) — reflects systemic and vascular inflammatory processes.

Markers of neural and glial injury

• NfL (neurofilament light chain) — well-established marker of axonal damage.
• GFAP — astrocytic injury and chronic neuroinflammation.
• APLP1 — marker of synaptic stress and neuronal functioning.
• SERPINA9 — reflects B-cell activity in germinal centers.
• FLRT2 — associated with tissue remodeling and cell adhesion.
• PRTG — involved in neuronal development and long-term structural outcomes.
• CNTN2 — reflects axonal–myelin integrity.

Marker of myelin biology

• MOG (myelin oligodendrocyte glycoprotein) — indicates myelin-related processes and demyelination/remyelination activity.

Together, these biomarkers provide a high-resolution biological picture of MS activity that cannot be derived from any single laboratory parameter.

Scientific Evidence Supporting the MSDA Test

1. Analytical validation

The study by Qureshi et al. demonstrated high precision, reproducibility, and robustness of the 18-protein panel across multiple analytical conditions.

2. Clinical validation

Chitnis et al. evaluated the MSDA Test in more than 600 MS patients. The Disease Activity Score strongly correlated with:

• gadolinium-enhancing (Gd+) MRI lesions,
• new or enlarging T2 lesions,
• clinical assessments of active vs. stable disease.

The multi-protein model significantly outperformed single biomarkers such as NfL.

3. Real-world clinical utility

Studies including Sanchez et al. showed that MSDA Test results influenced clinical decision-making — therapy initiation, switching, or confirmation of efficacy — in a meaningful proportion of patient visits.

Other research demonstrated that MSDA biomarker patterns correlate with:

• physical disability outcomes,
• cognitive decline,
• MRI-based structural measures.

How the MSDA Test Is Used in Practice

The test is most commonly used:

• at baseline, when initiating therapy,
• 3–6 months after changing treatment,
• every 6–12 months during long-term follow-up,
• in situations where symptoms and MRI findings do not fully match,
• when evaluating the need for escalation or de-escalation of therapy.

The frequency of testing is individualized and determined by the treating neurologist.

Availability and Cost

The MSDA Test is performed exclusively in the Octave Bioscience CLIA-certified and CAP-accredited laboratory (Menlo Park, CA).

It is fully authorized for use in all 50 U.S. states, including New York State (CLEP-approved).

It is classified as a Laboratory Developed Test (LDT) — regulated under CLIA rather than FDA.

Insurance coverage varies, but many U.S. patients pay a reduced out-of-pocket cost through the Octave Cares program.

Outside the United States (including Europe and Israel), the test is not yet widely available.

Who May Benefit Most from the MSDA Test

The MSDA Test may be particularly helpful for:

• patients wishing to closely monitor their disease activity,
• individuals in whom symptoms and MRI findings do not align,
• people considering therapy escalation or switching,
• patients on highly effective therapies where objective activity monitoring is essential,
• participants in clinical trials.

Key Takeaways for Patients

• The MSDA Test is a modern blood test analyzing 18 biomarkers with support from AI algorithms.
• It provides a quantitative, biological assessment of MS activity.
• It complements MRI and clinical examination but does not replace them.
• Research demonstrates strong correlations with MRI activity and real-world clinical outcomes.
• It supports personalized treatment decisions and may help detect disease activity earlier.

References

Qureshi F. et al. Analytical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis. Proteomics Clin Appl. 2023.
DOI: https://doi.org/10.1002/prca.202200018

Chitnis T. et al. Clinical validation of a multi-protein, serum-based assay for disease activity in MS. Clinical Immunology. 2023.
DOI: https://doi.org/10.1016/j.clim.2023.109688

Sanchez A. et al. Real-world clinical utility of a multi-protein, blood-based biomarker assay for MS disease activity. MSJ Exp Transl Clin. 2025.
DOI: https://doi.org/10.1177/20552173251331030

Gonyou T. et al. Proteomic biomarker panel for gauging MS disease activity: case series from real-world use. Int J MS Care. 2025.
DOI: https://doi.org/10.7224/1537-2073.2023-094

Zhu W. et al. Association between multi-protein serum biomarkers and disability in MS. Brain Commun. 2024.
DOI: https://doi.org/10.1093/braincomms/fcad300

Octave Bioscience / Olink technical documentation.