Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Neurofilament makes light of MS treatment monitoring

Serum levels of neurofilament light chain (NfL) can be used to monitor treatment responses and safety in multiple sclerosis (MS), according to two new studies. The findings indicate that NfL could be used to identify patients with a poor response or who are developing serious adverse effects.

NfL is a neuronal structural protein that is released following neuroaxonal damage, and previous work has demonstrated that NfL is a promising biomarker of MS disease activity and progression. Jens Kuhle and colleagues have now taken this work one step further.

“Several studies have shown that NfL is increased in cerebrospinal fluid and blood as a function of relapse activity of MS,” explains Kuhle. “Whether NfL levels would decrease under therapy was an obvious next question.”

To address this question, Kuhle and colleagues analysed NfL levels in serum samples from 589 participants in two phase III clinical trials of fingolimod in relapsing–remitting MS: the placebo-controlled FREEDOMS trial and the IFNβ1a-controlled TRANSFORMS trial. Serum samples were collected at baseline and at 6, 12, 18 and 24 months in FREEDOMS, and at baseline and 12 months in TRANSFORMS. NfL levels were measured with the single molecule array (SIMOA) immunoassay.

As previously shown, higher baseline serum levels of NfL were associated with greater disease activity. However, the new analysis also demonstrated that NfL levels were significantly lower at all time points in patients who received fingolimod than in patients who received placebo or IFNβ1a. By the end of the studies, levels approached those in healthy controls.

“We have, for the first time, a biofluid marker at hand that measures drug response in MS,” says Kuhle. “The icing on the cake is that the clinical experience that fingolimod is more potent than IFNβ1a is reflected by the degree of decrease in NfL.”

Nevertheless, more work needs to be done to develop NfL as a biomarker for use in individual patients. “Our next endeavour is to establish age-related normal values,” Kuhle says. “Standardization and refinement of the assay platform is another aspect.”

In the second new study, serum NfL levels were investigated as a marker of progressive multifocal leukoencephalopathy (PML), a rare but serious adverse effect of natalizumab treatment. Led by Giancarlo Comi, the researchers analysed serum NfL levels in 161 natalizumab-treated patients with MS, 25 of whom had PML, and 151 untreated patients with MS.

Onset of PML was associated with a tenfold increase in serum levels of NfL. Furthermore, among patients receiving natalizumab, serum levels of NfL could be used to discriminate between patients who were developing PML and those who were not, and between patients who were developing PML and those who were experiencing an MS relapse.

“We have, for the first time, a biofluid marker at hand that measures drug response”

“If validated in larger cohorts of patients, serum levels of NfL may be used as a biomarker to monitor not only drug efficacy, but also the occurrence and early recognition of PML,” the authors conclude in the paper.


Original articles

  1. Kuhle, J. et al. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology (2019)

    Article  PubMed  Google Scholar 

  2. Dalla Costa, G. et al. Serum neurofilaments increase at PML onset in natalizumab-treated MS patients. Ann. Neurol. (2019)

    Article  PubMed  Google Scholar 

Further reading

  1. Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577–589 (2018)

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Ian Fyfe.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fyfe, I. Neurofilament makes light of MS treatment monitoring. Nat Rev Neurol 15, 188 (2019).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing