Modern therapies have transformed care for people with multiple sclerosis (MS). Yet the disease continues to progress in a substantial proportion of patients, even in the absence of relapses. Detecting and treating this gradual worsening of disability remains one of the greatest challenges in MS care. Researchers from the University of Basel, Switzerland, now report on a blood marker that could help track disease progression and monitor treatment response.
Relapses are only part of the disease process in MS. In some patients, physical and cognitive abilities continue to gradually decline even in the absence of relapses. Experts refer to this as progression independent of relapse activity (PIRA). This process develops slowly and is difficult to detect and quantify. A currently available blood test measures neurofilament light chain (NfL ), a biomarker that mainly reflects neuroaxonal damage caused by acute inflammatory disease activity. A blood marker that captures the progressive component of the disease has so far been lacking.
"One of the key questions for us was whether progression leaves a different biological fingerprint than inflammation," says Professor Jens Kuhle from the University of Basel and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) at the University Hospital Basel. "If these processes are biologically distinct, we also need biomarkers that reflect different aspects of the disease rather than expecting a single marker to capture everything."
An additional MS biomarker
To investigate this question, researchers led by Jens Kuhle analyzed more than 18,000 blood samples and clinical data from more than 2,300 people with MS participating in two of the world's largest long-term MS cohorts in Switzerland and the United States. In the journal JAMA Neurology, the team reports that elevated levels of glial fibrillary acidic protein, or GFAP, were associated with the risk of disability progression in both the short and the long term. GFAP is a protein released by astrocytes, specialized support cells in the brain, when they become activated or injured.
The established biomarker neurofilament light chain (NfL) provided different information: it mainly reflected inflammatory disease activity and was associated with the risk of subsequent relapses. Together, the two biomarkers could therefore offer a more complete picture of the disease.
Changes during treatment may predict later progression
The researchers also found that patients whose GFAP levels declined after starting a treatment designed to slow the course of MS had a lower risk of future disability progression. Repeated measurements of the biomarker could therefore help monitor disease progression and treatment response over time.
"What was particularly noteworthy was not only that higher GFAP levels were associated with gradual disease progression," says Maximilian Einsiedler, one of the first authors of the publication. "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."
The study confirms previous findings, substantially strengthens the evidence supporting GFAP as a biomarker of progression independent of relapse activity and brings GFAP a step closer to clinical implementation . In the future, the biomarker could help monitor disease progression, assess treatment response, and accelerate the development of new therapies targeting progressive disease.
