Multiple sclerosis diagnosis is becoming more precise thanks to new insights into how the brain's immune system responds to MS damage. Scientists at the Paris Brain Institute have discovered that activation of microglia, the brain's resident immune cells, serves as a reliable biomarker for predicting how quickly a patient's disability will progress. This finding could transform how doctors diagnose MS and tailor treatments to individual patients.

How Is Multiple Sclerosis Currently Diagnosed?

Diagnosing MS has traditionally relied on a combination of neurological symptoms and imaging evidence. Doctors look for inflammatory plaques visible on MRI scans that show both spatial dissemination, meaning damage across different regions of the central nervous system like the brain, spinal cord, and optic nerve, and temporal dissemination, meaning lesions of different ages that appear over time.

The challenge is that MS symptoms vary dramatically from person to person. Some patients experience rapid disability progression while others remain relatively stable for years. This variability has made it difficult for doctors to predict outcomes and choose the most effective treatment strategies early on.

What New Biomarker Could Improve MS Diagnosis?

The team led by Professors Catherine Lubetzki and Bruno Stankoff at the Paris Brain Institute has made a significant breakthrough. They found that the activation of microglia in MS lesions is a reliable biomarker of disability progression. Microglia are immune cells that live in the brain and respond to damage by becoming activated. By measuring this activation on imaging, doctors may be able to predict which patients will experience faster disability progression and which will progress more slowly.

"The activation of microglia, the brain's resident immune cells, in lesions is a reliable biomarker of the progression of patients' disability. These results offer significant hope for adapting treatment for multiple sclerosis patients, evaluating new therapies, and reducing the severity of disability as much as possible," the research team noted.

Professors Catherine Lubetzki and Bruno Stankoff, Paris Brain Institute

This discovery addresses a critical gap in MS care. Currently, doctors monitor disease activity using the Expanded Disability Status Scale (EDSS), which measures disability severity, along with MRI scans and relapse frequency. However, these tools don't always predict which patients will develop progressive disability independent of relapses, a phenomenon called PIRA.

How Can Doctors Use These Insights to Personalize MS Treatment?

The implications of identifying microglia activation as a biomarker are substantial. Doctors could potentially use this information to:

• Predict Individual Outcomes: Measure microglia activation levels to forecast which patients are at highest risk for rapid disability progression and need more aggressive early treatment.
• Evaluate New Therapies: Use microglia activation as a measurable endpoint in clinical trials to determine whether experimental MS drugs are truly slowing neurodegeneration, not just reducing relapses.
• Reduce Disability Severity: Identify patients who would benefit most from high-efficacy disease-modifying therapies (DMTs) started early, potentially preventing irreversible damage before it accumulates.

This personalized approach is particularly important because recent research shows that early high-efficacy MS drugs are excellent at preventing relapses but may not address all forms of disability progression. A nationwide study in Denmark involving 3,316 adults with relapsing-remitting MS found that patients who started high-efficacy therapies early had a 75% lower risk of relapse-associated disability worsening compared to those who started with moderate-efficacy drugs and escalated later.

However, the same study revealed a significant therapeutic gap: early high-efficacy drugs did not significantly prevent PIRA, the type of disability that gradually accumulates even when relapses don't occur. After four years, 86.1% of patients who started high-efficacy drugs remained free of PIRA, compared with 84.4% in the escalation group, a difference that was not statistically significant.

What Does This Mean for MS Patients Right Now?

The discovery of microglia activation as a biomarker doesn't change treatment recommendations immediately, but it opens doors for future improvements. Researchers concluded that "the inflammatory activity expressed by relapses and the neurodegenerative progression reflected in PIRA represent partially independent mechanisms requiring potentially different therapeutic approaches," highlighting an unmet need for therapies that specifically target PIRA.

Meanwhile, the MS treatment landscape continues to evolve. Oculis, a biopharmaceutical company, recently treated the first patient in the PIONEER-1 registrational trial evaluating Privosegtor, a novel neuroprotective therapy for optic neuritis, a condition often linked with MS. Privosegtor is designed to cross the blood-brain and retinal barriers to preserve nerve function and potentially improve visual outcomes. The trial aims to determine whether this neuroprotective approach can achieve at least a 15-letter gain in vision, a meaningful improvement for patients.

The convergence of better diagnostic biomarkers like microglia activation and new neuroprotective therapies suggests that MS care is moving toward more precise, personalized treatment strategies. By understanding which patients are at highest risk for rapid progression and developing drugs that target different disease mechanisms, researchers hope to reduce the long-term disability burden of this complex neurological condition.