MS: Blood test may predict worsening disability 2 years early

According to Dr. Ari J. Green, chief of the Division of Neuroimmunology and Glial Biology and medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center at the University of California at San Francisco (UCSF), and co-senior author of this study, the biological basis for permanent irreversible neurological dysfunction is the loss of connections within the nervous system.

“Progressive disability worsening in MS is likely caused by the cumulative effect of the loss of tens of thousands or even millions of axons and connections from the critical circuits that underlie our essential neurological functions,” Dr. Green explained to Medical News Today.

“However, viewed this way, the loss of neurological function in the context of progressive worsening is a terminal event without the capacity for reversal. Waiting until someone shows this worsening leaves us unable to do anything that would stop it. Therefore, finding ways to detect neurological worsening in advance of it happening in MS gives us hope that we can do something to stop or reverse the process,” he continued.

For the blood test, the researchers focused on using the neurofilament light chain (NfL) as the blood biomarker.

“Neurofilament light chain is one of a number of special proteins found mainly in nerve fibers,” Dr. Ahmed Abdelhak, a physician-scientist and clinical instructor in the Division of Neuroimmunology and Glial Biology at the University of California at San Francisco (UCSF), and co-first author of this study, told MNT.

“When nerve fibers (axons) get damaged or lost, some of this protein — or short segments called peptides — find a way to enter the blood,” he explained.

“We can measure this tiny fraction with an ultrasensitive technique known as a digital immunoassay — specifically a single molecule array — that can measure proteins or peptides like this at extraordinarily low concentrations,” Dr. Abdelhak continued.

“Therefore, in some ways, NfL becomes an important marker to measure for evidence of injury to nerve fibers. It doesn’t detect symptom worsening as much as it predicts future worsening of function that creates the symptoms patients experience,” he said.

For this study, Drs. Green and Abdelhak and their team analyzed data from about 1,900 people with multiple sclerosis. Of that number, about 570 were classified with a disability that continued to worsen, with the majority independent of relapses.

A relapse — also called a flare-up — happens when new symptoms occur, or old symptoms worsen.

Researchers found that elevated NfL levels were associated with up to a 91% higher risk of worsening disability with relapse about a year later. Elevated NfL levels were linked to a 49% increased risk of worsening disability without relapse nearly two years later.

Dr. Green said they were shocked by both findings, especially their magnitude and how long in advance they could see changes.

“First, we think relapses in MS are a relatively acute event that occurs over a few days. Traditionally we have thought that the immune system inappropriately gets turned on and attacks a small local area in the brain, optic nerve, or spinal cord,” he continued.

“However, this work suggests there are things happening either locally at the site of the future relapse or more globally across the brain that show damage to nerve fibers before people with MS will develop permanent disability following a relapse. This process is critical for us to understand as it may suggest a paradigm shift in the way we think about relapses resulting in permanent disability specifically and MS injury in general,” Dr. Abdelhak added.

“In the [MS] patients with progression but without relapses the changes were happening even earlier — which gives us the potential that there is time to do things that might reverse or stop progression.”
— Dr. Ahmed Abdelhak

After reviewing this study, Dr. Lana Zhovtis Ryerson, research director at the Hackensack Meridian Neuroscience Institute at Jersey Shore University Medical Center – Multiple Sclerosis (MS) Center, told MNT it is very exciting to see a biomarker that can predict disability one to two years before occurrence.

“This is a biomarker that we are starting to monitor in our clinic and provides evidence that longitudinal monitoring of this data point can make a difference in our patient population,” Dr. Ryerson continued.

“MS therapies are most effective in preventing relapses and to a lesser extent disability. We have no effective ways to improve disability so we really aim at prevention in MS. This biomarker allows for this to occur.”
— Dr. Lana Zhovtis Ryerson

And Dr. Bruce F. Bebo, Jr., executive vice president of research at the National Multiple Sclerosis Society, told MNT that being able to predict the course of disease in an individual with MS would greatly help in selecting the most appropriate disease-modifying therapy for an individual.

“Currently, there is little information available to help guide the choice of disease-modifying therapy,” Dr. Bebo explained.

“This information would help the doctor and patient make an informed decision regarding therapy choice. We know that there are tremendous benefits for getting someone on an effective therapy for them and a biomarker like sNfL could help people get on an effective treatment sooner,” he said.