Multiple Sclerosis Progression Through Blood: How GFAP and NfL Redefine Disease Monitoring
Multiple sclerosis (MS) is often described as a disease of two faces. Many patients begin with a relapsing-remitting form, marked by episodes of inflammation and symptom flare-ups that partially or fully recover. Over time, however, a subset transitions into a progressive phase — a steady worsening of disability, independent of relapses. Another 20% start in this progressive stage right from diagnosis, known as primary progressive MS.
This progression represents a profound shift in disease biology: from inflammation driven by immune cells attacking the nervous system to a self-sustaining neurodegenerative process rooted within the brain and spinal cord. Detecting when this transition happens — and identifying which patients are truly “progressing” — has been one of the toughest challenges in MS research and care.
That’s where the study by Christian Barro and colleagues at Harvard Medical School and Brigham and Women’s Hospital comes in. Their research points to two promising blood biomarkers that can help decode the hidden biology of MS progression.
The Two Blood Clues: sNfL and sGFAP
The team focused on two proteins measurable in blood:
Neurofilament light chain (sNfL): a marker of neuronal injury, reflecting damage to nerve fibers.
Glial fibrillary acidic protein (sGFAP): a marker of astrocytic activation, reflecting the scarring and support-cell changes that accompany chronic neurodegeneration.
Both proteins can now be detected in serum using ultra-sensitive single-molecule assays, offering a noninvasive window into brain health.
But what do they really tell us about MS?
The Study Design: Mining Decades of MS Data
Researchers leveraged data from the Comprehensive Longitudinal Investigation of MS at Brigham and Women’s Hospital (CLIMB) — a massive natural history study spanning over 20 years of clinical visits, MRI scans, and blood samples.
They analyzed 257 patients who had reached at least EDSS 3 (a level of noticeable disability on the Expanded Disability Status Scale). These patients were at high risk of progressive pathology. Each provided a blood sample within six months of reaching that threshold, and they were followed for a median of 7.6 years.
Patients were categorized by:
Progression: Did they experience 6-month confirmed disability progression (6mCDP)?
Activity: Did they have new MRI lesions or relapses — indicating “active” disease — in the two years before or after baseline?
What the Data Revealed
1. sNfL Tracks Inflammatory Activity
Patients who had recent relapses or MRI activity showed elevated sNfL levels. This confirmed its role as a biomarker of acute inflammatory damage. sNfL rose during active disease but wasn’t linked to long-term progression.
For example, sNfL levels were significantly higher in patients with disease activity in the two years before or after baseline (p < 0.05).
2. sGFAP Reflects Chronic Progression
In contrast, higher baseline sGFAP levels predicted future disability progression, especially in patients who did not have active inflammation.
Each standard deviation increase in sGFAP raised the risk of confirmed disability progression by 71% (HR = 1.71; p = 0.004).
The association was strongest in patients with low sNfL, suggesting that astrocytic activation — not inflammation — drives worsening in nonactive, progressive disease.
3. Complementary Signals
While sNfL and sGFAP were moderately correlated (r = 0.42), their clinical meanings diverged:
sNfL = ongoing damage from inflammation
sGFAP = underlying degeneration and scarring
Together, they provide a dual lens on MS pathology — one focused on “fire” (inflammation), the other on “ash” (progression).
Why This Matters for MS Research and Treatment
This study is more than an academic exercise — it has real-world implications for how we design and interpret MS trials.
Precision in trial recruitment: sGFAP could help identify patients with nonactive progressive MS, a group that often fails to respond to anti-inflammatory drugs but could benefit from neuroprotective or remyelinating therapies.
Monitoring disease biology: sNfL may serve as a dynamic marker of acute disease control, while sGFAP could track the slow burn of progression.
Toward personalized MS care: Instead of rigidly classifying patients as “progressive” or “not,” clinicians could use these biomarkers to map where each patient lies on the MS continuum.
As lead author Dr. Tanuja Chitnis explains, these biomarkers may allow physicians to “define a patient’s degree of progressive pathology rather than simply labeling them as progressive MS or not.”
Limitations and Next Steps
Like all real-world studies, this one had caveats. The patients were at varying stages of disability, and treatment exposure wasn’t randomized. Still, the long follow-up and robust sample handling make the results compelling.
Future research will likely explore:
Combining sGFAP and sNfL with MRI metrics or other fluid biomarkers.
Establishing sex- and age-adjusted reference ranges, since sGFAP was found to be higher in women and both markers rise with age.
Validating these results in multicenter trials and therapeutic studies targeting neurodegeneration.
The Takeaway
Serum GFAP and NfL levels tell complementary stories about MS:
sNfL signals active, inflammatory damage.
sGFAP reveals silent, progressive degeneration.
By bringing these insights together, researchers are edging closer to biological precision in how we understand, monitor, and treat multiple sclerosis.
As this study elegantly shows, sometimes the most powerful insights into the brain’s complexity can be found not in an MRI, but in a few drops of blood.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Barro C., Healy B.C., Liu Y., Saxena S., Paul A., Polgar-Turcsanyi M., et al. Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients with Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023;10:e200052. doi:10.1212/NXI.0000000000200052
