Scientists have identified a blood marker that could help doctors track the slow, silent progression of multiple sclerosis (MS) and monitor whether treatments are working – even in patients who are not experiencing relapses.
The discovery, led by researchers at the University of Basel in Switzerland, focuses on a protein called glial fibrillary acidic protein (GFAP), which is released by astrocytes, support cells in the brain, when they are activated or damaged.
In a study, the team found that higher levels of GFAP in the blood were linked to a greater risk of disability progression over both the short and long term.
MS is best known for causing relapses, sudden flare-ups of symptoms followed by periods of recovery.
But for many patients, the disease also grinds on quietly in the background, with disability worsening gradually even when no relapse has occurred.
Clinicians call this “progression independent of relapse activity”, or PIRA.
Because it develops slowly and unfolds without obvious flare-ups, it is notoriously hard to detect and measure, making it one of the toughest problems in modern MS care, despite huge advances in treatment over the past two decades.
Until now, the main blood-based tool available to clinicians has been a marker called neurofilament light chain (NfL), which reflects damage to nerve fibres caused by acute inflammation.
But NfL does not appear to capture this steadier, inflammation-independent decline, leaving a gap in doctors’ ability to monitor the progressive side of the disease.
To address that gap, the Basel team, led by Professor Jens Kuhle, analysed more than 18,000 blood samples alongside clinical data from over 2,300 people with MS, drawing on two of the largest long-term MS patient cohorts in the world, based in Switzerland and the United States.
Kuhle said the research set out to establish whether the biological signature of gradual progression was actually distinct from that of inflammation.
If the two processes were shown to be biologically separate, he said, that would point to the need for different biomarkers capturing different aspects of the disease, rather than relying on a single measure to do it all.
The results suggested a clear division of labour between the two markers.
While NfL tracked inflammatory activity and predicted the likelihood of future relapses, elevated GFAP levels were tied specifically to the risk of disability progression. Used together, the researchers say, the two markers could give clinicians a fuller picture of how a patient’s disease is behaving.
The study also found that GFAP levels could carry predictive value over time. Patients whose GFAP fell after starting disease-modifying treatment had a lower risk of going on to develop worsening disability — suggesting repeated testing could be used to monitor how well a treatment is working, not just take a one-off snapshot.
Maximilian Einsiedler, one of the study’s first authors, said: “What was particularly noteworthy was not only that higher GFAP levels were associated with gradual disease progression.
“Changes in the biomarker during treatment were also associated with patients’ later risk of disability progression.
“This suggests that GFAP may capture more than a snapshot of disease activity and reflect biological processes that influence the future course of the disease.”
