Blood Biomarker Predicts Multiple Sclerosis Progression

Researchers discovered that elevated levels of NfL in the blood of Multiple Sclerosis patients could indicate deteriorating impairment during the next one to two years. This groundbreaking study identifies a critical timeframe for potential therapies.

The team discovered that high NfL levels were linked with a considerable risk of disability progression, with or without relapse, after reviewing data from over 1,900 individuals over a decade.

These findings highlight the significance of NfL as an early biomarker for nerve injury and may open the path for early therapy of MS.

According to a recent study led by UC San Francisco researchers, people with multiple sclerosis who have high NfL, a biomarker of nerve injury, may experience greater disability one to two years later.

According to co-first author Ahmed Abdelhak, MD, of the UCSF Department of Neurology and the Weill Institute for Neurosciences, the study is the first to measure the timeframe preceding disability worsening in which injury to the central nervous system occurs.

MS affects about 1 million Americans. Patients with advanced cases may have reduced movement, as well as stiffness, weakness, poor coordination, and incontinence. Recent advancements, however, imply that more severe symptoms can be significantly postponed or even avoided.

“This rising of NfL up to two years before signs of disability worsening, represents the window when interventions may prevent worsening,” said Abdelhak.

The researchers looked at the incidence of disability worsening, defined as six months or more of increased impairment reflected in a higher score on the Expanded Disability Status Scale, in the study, published in JAMA Neurology on Nov. 6, 2023.

They differentiated between disability increasing with recurrence, which includes remaining symptoms or the return of old ones after relapse, and progressive advancement of symptoms without relapse.

91% are at high risk of disability deterioration.

The researchers analyzed data from around 4,000 patient visits to UCSF in the EPIC study and nearly 9,000 patient visits to different sites in Switzerland in the SMSC study over a 10-year period.

The two investigations involved over 1,900 patients in total. 570 people were recognized as having a disability that was worsening, with the majority being independent of relapses.

Researchers discovered that elevated NfL levels were related with a 91% greater chance of deteriorating impairment with relapse almost a year later, and a 49% higher risk of worsening disability without relapse nearly two years later.

“We think that NfL elevation occurs earlier in disability worsening without relapse,” said Abdelhak. This different pattern may indicate “a more prolonged process that decreases in intensity in advance of increased impairment,” said co-senior author Ari Green, MD, medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center.

“This aligns with a recognition that death of nerve cells is a slow process that builds toward permanent disability and means that interventions to protect nerve cells might have time to also stop disability,” he said.

“In addition to the groundbreaking findings on the temporal relationship between NfL increases and gradual disease progression in MS, the study supports the important role of NfL as an early marker of nerve damage,” said co-senior author Jens Kuhle, MD, PhD, who led the Swiss cohort and is head of the Multiple Sclerosis Center at University Hospital and University of Basel, Switzerland.

“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” he said.

Future research will explore into therapies that can halt progression during this phase of high NfL.

For more information: Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis, JAMA Neurology

doi:10.1001/jamaneurol.2023.3997