High Levels of NfL Protein Linked to Disability, Faster Disease Progression in MS

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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KIF5A Protein, potential biomarker, progressive MS

High levels of neurofilament light chain (NfL) protein circulating in the blood of patients with multiple sclerosis (MS) at an early stage of the disease are linked to higher disability and faster disease progression, a study has found.

According to researchers, these findings suggest that NfL — a protein commonly used as a marker of nerve cell degeneration in neurodegenerative disorders — could be a useful prognostic marker for MS, helping physicians select the best course of treatment for each patient.

Findings were reported in the study, “Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis,” published in the journal Nature Scientific Reports.

MS is an autoimmune, neurodegenerative disorder for which both short- and long-term prognosis are difficult to ascertain. While some patients remain well for many years without treatment, others progress rapidly and fail to respond to therapies.

“In this context, accurate early prognostication is even more important … [because] if we can identify patients with more aggressive MS early on, we may be able to alter the trajectory of the disease, preventing or delaying the accrual of disability,” investigators wrote.

Currently there are no established biomarkers that physicians can use to assess the severity of MS, or to select the best course of treatment for each individual patient.

However, recent studies have suggested the levels of NfL — a protein normally released by nerve cells upon injury — in the patients’ blood serum are correlated with MS activity, indicating NfL possibly may be used “as a surrogate for disease severity, recent disease activity and treatment response,” the team wrote.

To investigate the value of NfL as a prognostic biomarker of MS, researchers at the University of Ottawa in Canada reviewed the medical records of 67 patients who had their serum NfL levels measured at an early phase of the disease (near onset), and correlated these findings with their long-term clinical outcomes.

All patients included in the study provided blood samples within five years of experiencing their first MS symptoms, and all were followed for more than 15 years (median follow-up of 18.9 years).

Serum NfL levels were measured in patient blood samples, as well as in samples taken from 37 individuals of the same age and sex who did not have MS (control group). Statistical analyses were used to identify possible relationships between serum NfL levels and patients’ long-term clinical outcomes.

At baseline, MS patients had a median serum NfL level of 10.1 picograms per millilitre (pg/mL), which was 38.5% higher than that seen in individuals without the disease (7.26 pg/mL).

Statistical analyses indicated that patients whose serum NfL levels were lower than 7.62 pg/mL were 4.3-times less likely to experience severe disability (EDSS score of 4 or higher), and 7.1-times less likely to develop a progressive form of the disease.

Conversely, in those whose serum NfL levels were higher than 13.2 pg/mL, MS progressed much more rapidly, with EDSS scores increasing on average 0.16 points per year. (The higher the EDSS score, the greater the patient’s disability). These findings held true even after investigators adjusted data to take into account patients’ age, sex, and use of disease-modifying therapies.

“This study demonstrates that baseline sNfL is associated with long term clinical disease progression. sNfL may be a sensitive marker of subsequent poor clinical outcomes,” researchers wrote. “We found that serum NfL cutoff of 7.62 pg/mL was the discriminator of future disease progression.”

According to the team, “one day, multimodal prognostic indices including clinical, MRI and serological data (such as NfL …) may assist in the identification of high-risk patients who may benefit the most from early aggressive therapies. Conversely, patients identified as having a very good prognosis may not require treatment at all, or will choose the safest and more modestly effective treatments.”

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