Bruce Hughes, MD, provides an overview of the use of neurofilament light chain (NfL) as a biomarker in multiple sclerosis (MS), highlighting the accuracy and reliability of plasma/serum NfL (pNfL) and cerebrospinal fluid (CSF) NfL measurements.
Bruce Hughes, MD: Biomarkers have been used for a long time in the diagnosis and, more recently, monitoring of disease progression in multiple sclerosis. With regard to biomarkers at the diagnosis of multiple sclerosis, it’s limited to MRI scans, cerebral spinal fluid [CSF] analyses, and evoked potentials. Regarding monitoring, because of the invasive nature of CSF studies and inaccuracies of evoked potentials, for monitoring disease progression, the biomarker that’s been used has been MRI scans. It leaves a lot missing in helping us monitor patients.
Neurofilament light chain [NfL] is a family of highly conserved neuron-specific structural proteins that we’ve known about for decades. For years we’ve been assessing this in spinal fluid, and we’ve known that spinal fluid levels of NfL can be markers of central nervous system neuronal damage. Over the past few years, we’ve been able to correlate the serum and plasma levels of NfL with the CSF levels. This is a much less invasive way to make determination of levels without having to do repetitive spinal taps on patients. Plasma and serum NfL levels are used somewhat interchangeably, but they will be discussing mostly serum NfL levels because you can detect NfL in plasma and serum. The correlation isn’t as good, and it’s a little more tricky detecting it in plasma. The assays are easier in serum. Moving forward, we’ll be talking about how it’s used interchangeably and, more specifically, about serum NfL levels.
Over the past few years, we’ve developed serum measures by a variety of ultrasensitive single-molecule detection assays. These include Simoa, ELISA, and other arrays and ways of determining serum NfL levels. Study after study has looked at the correlation between these assays and the CSF assays; the correlation has been very high. When monitoring patients, you don’t want to do repetitive lumbar punctures to determine, with this invasive test, how they are doing. Instead, a simple serum test can give you that answer. More recently, the prices of the assays have come down.
Over the past few years, we’ve had published data looking at a variety of aspects and applicabilities of serum NfL. A couple of years ago, Stefan Bittner and colleagues looked at the benefits of serum NfL in diagnostic accuracy but also disease progression. They showed that patients who were at the beginning with clinically isolated syndrome, had lower levels of NfL compared with patients who had demonstrated a relapsing phase of the disease process. They also showed that this correlation of higher levels could translate to relapse rate and MRI progression. Other studies, like the 1 led by Ester Cantó, looked more at monitoring disease progress. Here you had substantiation where higher levels of NfL translated into worsening disability, MRI measures, and relapses. Most recently, as of April, in JAMA Neurology, the Enric Monreal group looked at a large number of patients at onset and followed them. At diagnosis, patients had NfL levels checked. Higher levels translated into higher chances of disability progression down the road. The implication by the authors was that higher levels of NfL may be in individuals where treaters would want to use more highly effective therapies at onset.
Transcript edited for clarity