Two-protein blood test may better track MS activity, disability

Long-term analysis links GFAP and NfL to MS progression and relapses

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In this illustration, a dropper squirts blood alongside four half-filled vials.
  • GFAP and NfL blood levels help track MS disease activity and disability progression.
  • NfL is linked to relapse risk, while GFAP signals disability progression (PIRA).
  • Using both markers may help personalize MS care and flag higher-risk patients.

Simultaneously measuring levels of two blood proteins — glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) — may offer a clearer way to track both disease activity and disability progression in people with multiple sclerosis (MS), according to a new long-term study.

Each marker is tied to a different clinical outcome: NfL helps predict relapse risk, while GFAP is more closely linked to disability progression that happens independently of relapses (PIRA). Used together, the two-protein panel may help identify patients at higher risk for worsening outcomes and support more personalized treatment decisions.

That’s according to the study, “GFAP and NfL as predictors of disease progression and relapse activity in fingolimod-treated multiple sclerosis,” published in Brain. The work was funded by the Swiss National Science Foundation and the pharmaceutical companies Merck, Roche, and Novartis.

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How GFAP and NfL reflect different aspects of MS disease activity

In most people with MS, the disease is marked by relapses — periods when symptoms suddenly worsen — followed by remissions, when symptoms ease. People with relapsing forms of MS can develop long-term worsening of disability from incomplete relapse recovery, but many also experience a gradual worsening of symptoms that happens independently of relapses, a process known as PIRA.

GFAP and NfL are established markers of nervous system damage: elevated NfL reflects injury to nerve cells, while elevated GFAP indicates inflammatory activation of astrocytes — star-shaped support cells in the brain and spinal cord.

Previous studies suggest that both NfL and GFAP can serve as valuable MS biomarkers. Elevated NfL is linked to relapses, while higher GFAP levels are associated with PIRA. However, there’s limited data on how GFAP responds to MS treatments.

To address this gap, researchers analyzed clinical data from 420 people with relapsing MS who were treated with Gilenya (fingolimod), an oral therapy that reduces disease activity by preventing immune cells from entering the nervous system.

They were followed for a median of 9.1 years, during which nearly 3,000 blood samples were collected. Samples from thousands of people without MS were also analyzed for comparison, since NfL and GFAP levels naturally vary with factors such as age, sex, and body mass index (BMI), a measure of body fat based on weight and height.

Higher early GFAP levels tied to later disability progression in treated patients

Over the course of follow-up, about one-third of patients experienced PIRA. Statistical analyses showed that people with higher GFAP levels during the first year on Gilenya were significantly more likely to experience PIRA. Analyses also showed that increases in NfL were linked to relapses, consistent with earlier studies.

These findings suggest that GFAP and NfL together provide complementary information for monitoring disease activity and progression in people with MS who are taking Gilenya, the researchers said.

The tests used to measure GFAP and NfL in this study were developed by Quanterix, which was not directly involved in the research. In a company press release, Masoud Toloue, CEO of Quanterix, said the study “solidifies a new avenue for improving personalized therapy for MS patients.”

“Our platform’s ability to deliver both highly sensitive assays in a single multiplexed test along with the necessary normative data infrastructure makes these results immediately actionable for providers, offering a truly best-in-class approach to MS management,” Toloue said.