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The MSDA test (Multiple Sclerosis Disease Activity Test) is a multi-protein serum assay that simultaneously measures 18 protein biomarkers. Based on their combined pattern, a machine-learning algorithm calculates a quantitative index of multiple sclerosis disease activity.
The main purpose of the test is to provide additional objective information about disease activity between clinical visits and MRI examinations. MSDA does not replace neurological assessment or magnetic resonance imaging and is not used to diagnose MS on its own.
Multiple sclerosis is not a single biological process. Peripheral immune activation, neuroinflammation, myelin injury, axonal injury and glial responses can all occur at the same time.
No single biomarker can describe all of these aspects equally well. This is the idea behind MSDA: instead of measuring one molecule, the test analyzes a combination of several proteins.
Shows structural consequences of disease: new lesions, contrast-enhancing activity, spinal cord involvement and other anatomical changes.
Reflects neuroaxonal injury, but is not specific to multiple sclerosis.
Combines 18 serum proteins in a multidimensional model developed to estimate the likelihood of disease activity.
MSDA was developed by Octave Bioscience. The test uses serum. It simultaneously measures the concentrations of 18 proteins associated with different components of multiple sclerosis biology.
These values are not simply added together. They are processed by a dedicated algorithm that produces:
A numerical score from 1.0 to 10.0, divided into low, moderate and high categories of disease activity.
These describe four groups of processes: immunomodulation, neuroinflammation, myelin biology and neuroaxonal integrity.
Protein measurements use a proximity extension assay (PEA), a method designed for simultaneous high-sensitivity measurement of many protein molecules from a small volume of serum.
A serum sample is collected for measurement of 18 protein biomarkers.
The concentrations of each panel component are determined.
The values are processed by a multilayer machine-learning model (stacked classifier).
The report provides an overall Disease Activity Score and four Disease Pathway Scores.
Corresponds to the lowest probability of marked focal MRI activity in the validation model.
Associated with a higher probability of active inflammatory changes than the low category.
Associated with the highest probability of marked focal activity in the clinical validation dataset.
In the clinical validation, a moderate or high score was associated with approximately 4.49-fold higher odds of having at least one gadolinium-enhancing lesion than a low score.
A high score was associated with approximately 20.99-fold higher odds of having two or more gadolinium-enhancing lesions than the low and moderate categories combined.
These are statistical odds ratios from the study cohort, not an individual prediction of how many lesions a specific patient will necessarily have.
A combination of proteins associated with regulation of the peripheral immune response.
A group of signals associated with inflammatory processes related to the central nervous system.
A combination of measures associated with myelin and myelin injury.
A group of proteins associated with the state of neurons, axons and nervous tissue.
The panel is best viewed not as 18 separate laboratory tests, but as a set of input variables for one multidimensional model. For many individual components, stand-alone clinical interpretation has not been established.
| Protein | Full name | Biological context |
|---|---|---|
| APLP1 | Amyloid beta precursor-like protein 1 | Neuronal protein associated with synaptic and nerve-cell function. |
| CCL20 | C-C motif chemokine ligand 20 | Involved in recruitment and migration of immune cells. |
| CD6 | Cluster of differentiation 6 | T-cell surface molecule involved in activation and cell-cell interactions. |
| CDCP1 | CUB domain-containing protein 1 | Involved in cell adhesion and signaling; included in multidimensional MS activity models. |
| CNTN2 | Contactin-2 | Cell-adhesion molecule expressed in the nervous system and associated with axons and myelin. |
| CXCL13 | C-X-C motif chemokine ligand 13 | Important in B-cell migration and humoral immune activity. |
| CXCL9 | C-X-C motif chemokine ligand 9 | Associated with interferon-dependent immune activation and T-cell migration. |
| FLRT2 | Fibronectin leucine-rich transmembrane protein 2 | Involved in cell adhesion, signaling and nervous-system development. |
| GFAP | Glial fibrillary acidic protein | Astrocyte structural protein; also studied independently as a biomarker of astroglial activation. |
| IL-12B | Interleukin-12 subunit beta | Encodes the p40 subunit shared by IL-12 and IL-23, which participate in immune regulation. |
| MOG | Myelin oligodendrocyte glycoprotein | Protein on the outer surface of CNS myelin. Measuring MOG concentration in MSDA is not an anti-MOG antibody test and is not used to diagnose MOGAD. |
| NfL | Neurofilament light chain | Well-studied biomarker of neuroaxonal injury; not specific to MS on its own. |
| OPG | Osteoprotegerin | TNF-receptor-family protein involved in immune regulation, vascular biology and bone metabolism. |
| OPN | Osteopontin | Immunoregulatory protein associated with inflammatory processes and immune-cell activation. |
| PRTG | Protogenin | Molecule involved in development and differentiation of cells in the nervous system. |
| SERPINA9 | Serpin family A member 9 | Protein expressed, among other sites, in germinal-center B cells. |
| TNFRSF10A | TRAIL receptor 1 / TNF receptor superfamily member 10A | Receptor involved in apoptosis-related signaling and cell regulation. |
| TNFSF13B | B-cell activating factor BAFF / TNF superfamily member 13B | One of the key factors involved in B-cell survival and maturation. |
Several different types of MSDA studies have been published: candidate-protein discovery, analytical validation, clinical validation, studies of associations with different outcomes, and assessments of real-world clinical use.
Research cohorts evaluated more than 1,400 proteins and identified combinations associated with clinical and radiological MS activity.
Accuracy, reproducibility, sample stability and resistance of the method to analytical factors were assessed.
Of 21 candidate proteins, 18 met the criteria for inclusion in the final algorithm.
The algorithm was evaluated against contrast-enhancing activity, new or enlarging T2 lesions, and a combined classification of active versus stable MS.
The clinical validation analyzed 614 serum samples. Some were used to build the algorithm, while a separate test set was used to evaluate performance.
This was one of the main reference outcomes used to build the overall Disease Activity Score.
The MSDA score was also statistically associated with new or enlarging T2 lesions.
The multi-protein model was associated with a combined clinical-radiological classification of disease activity.
In the clinical validation, the multi-protein model performed better than a model based only on neurofilament light chain.
A separate 2024 study of 630 samples also found that multidimensional proteomic models described several clinical and radiological measures of activity better than individual proteins.
This is a separate question. Association with MRI does not automatically mean that using the test improves long-term outcomes. That is why studies of real-world clinical utility are important.
In a 2025 study, 20 physicians from 14 practices examined decisions made before and after receiving MSDA results.
After the test result became available, the clinical decision changed at 19.4% of evaluated time points.
Physicians reported that the test influenced decision-making in 59.8% of cases when one MSDA result was available and in 69.2% when several sequential results were available.
| Method | What it mainly shows | Main advantage | Main limitation |
|---|---|---|---|
| MRI | Focal activity, lesion location and structural changes | Main objective tool for MS monitoring | Performed periodically and does not reflect every biological process |
| Neurofilament light chain (NfL) | Neuroaxonal injury | Single quantitative blood biomarker convenient for serial measurement | Not specific to MS and does not identify the cause of injury |
| Glial fibrillary acidic protein (GFAP) | Astroglial activation | Of particular interest for studying PIRA and progressive biology | Not yet a universal routine decision-making tool |
| MSDA | Multidimensional profile associated primarily with inflammatory activity | Integrates 18 protein measures at the same time | Specialized commercial test; does not replace MRI and still has a more limited independent evidence base |
Serial MSDA measurements may complement clinical assessment and MRI when following response to therapy.
The test may be useful when the clinical picture does not provide a confident answer about how stable the disease really is.
A repeatable blood test can provide an additional time point for monitoring, but it does not prove that MRI can be omitted or performed much less often.
MSDA may be one element in the overall body of evidence, but not a stand-alone reason for escalation or de-escalation of DMT.
These are potentially some of the most interesting situations, but they require particularly cautious interpretation.
When was MRI performed, which protocol was used, were there clinical events, infections or other illnesses?
One high result and a persistent rise across several tests are not the same thing.
Discordant results are a reason to reassess the patient carefully, not an automatic instruction to change treatment.
There is currently no universal international recommendation for a mandatory MSDA testing interval. The interval should depend on the clinical question.
The manufacturer states that many patients in the United States repeat testing approximately every 3–6 months. This reflects how the test is used in US practice, but it is not an international standard of MS care.
Repeat testing may be considered once enough time has passed for the expected treatment effect to become apparent.
Frequency should depend on whether a new result would change monitoring or management.
Additional testing may be useful when clinical findings, MRI and expected treatment response do not agree.
The name of the test should be taken literally: Disease Activity. Its main clinical validation was built around markers of new inflammatory activity, especially contrast-enhancing lesions on MRI.
Although individual panel proteins, such as NfL and GFAP, are also associated with long-term injury and progression, the MSDA score itself should not be interpreted as a validated marker of PIRA or transition to SPMS.
MSDA is a commercially available laboratory test in the United States. It is performed in Octave Bioscience's clinical laboratory, which is CLIA-certified, CAP-accredited, and approved by the New York State laboratory program.
By 2025, the test had become available in all 50 states. After physician ordering, blood collection can be performed, among other options, through the broad Quest Diagnostics network.
Final out-of-pocket cost depends on insurance coverage and individual circumstances.
The ordering infrastructure described by the manufacturer is primarily US-based. MSDA is not a standard laboratory investigation routinely used in MS follow-up in Israel.
If the test is clinically relevant, the possibility of obtaining and internationally shipping a sample should be clarified individually.
The test was developed for people with multiple sclerosis and does not replace the McDonald diagnostic criteria.
MSDA does not show where a lesion is, and does not assess the spinal cord, cortex, atrophy or lesion morphology.
A low result does not exclude gradual disability accumulation without relapses.
There is no validated algorithm saying: “with this MSDA score, use this specific DMT”.
Repeat frequency should be determined by the clinical question, not by a mandatory international schedule.
Prospective studies are especially important to determine whether using MSDA improves long-term clinical outcomes.
It is necessary to understand how comparable the studies are, whether the biomarker is changing over time, and whether alternative explanations exist.
A laboratory test should not override reliable clinical or radiological evidence of activity.
A biomarker can add to the arguments for or against changing strategy, but the decision should also consider efficacy, safety and the patient's treatment history.
In this situation, assessment should not be limited to an inflammatory activity score. PIRA, the spinal cord, functional change and progressive disease biology also need to be evaluated.