| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
Neurofilament light chain test helps in diagnosis, treatment, and prognosis of ALS and MS
Eye on Innovation
By using a test that measures neurofilament light chain (Nfl) proteins in blood, clinicians can better diagnose devastating diseases like ALS and MS, help predict disease progression, and better assess efficacy of existing drugs and trial therapies.
The Neurofilament Light Chain, Plasma assay (Mayo ID: NFLP), launched by Mayo Clinic in April of 2022, measures minute concentrations of neurofilament light chain (NfL) proteins in the blood. When elevated, this protein can be a nonspecific marker for neurological conditions such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). This is because neuroaxonal damage releases NfL proteins into the blood as well as the cerebrospinal fluid.
Neurofilament light chains are an important structural building block of nerve cells. The protein helps maintain the shape and stability of neurons and circulates in everyone’s blood. “When you're first born, NfL concentrations are relatively high, then gradually decrease until age 14 or 15,” says Joshua Bornhorst, Ph.D., a consultant in Mayo Clinic’s Division of Clinical Biochemistry and Immunology, who led a comparison study on Nfl reference interval concentrations in blood in pediatrics and adults.
“Then they trend up by two or three percent each year for the rest of your life. People who are 90 may have five-fold higher levels than someone who’s 20 years of age. Ultimately, NfL concentrations in healthy individuals are strongly influenced by age and also by renal function,” says Dr. Bornhorst.
When these Nfl concentrations spike above their expected normal range for a given age, this can be a warning sign of neurological disease.
ALS patients typically exhibit two- to threefold increases of NfL in blood. Bjorn Oskarsson, M.D., director of the ALS Center of Excellence at Mayo Clinic in Jacksonville, Florida, was one of the first specialists to use the NFLP assay as part of his patient practice.
“Thanks to Mayo Clinic Laboratories, we were able to implement this test very early, and it is a test that has served us well,” says Dr. Oskarsson.
“Neurofilament testing is used diagnostically in ALS. It’s one of the pieces we use along with patient exam, history, EMG (electromyography), and there’s some new brain imaging techniques that have become more widely utilized in the last year. Each of these pieces complement each other and tell us a little different part of the story and together, they increase our confidence in an ALS diagnosis.”
The assay can also help measure the disease’s rate of progression and give the patient an idea of how much time they have left. “This might be information that some patients really want,” says Dr. Oskarsson. “Others might not want to know this information, so what we disclose is based on a dialogue with the patient.”
Further, the assay can help estimate the efficacy of drug therapies. If a patient’s NfL protein levels are going down, for example, the treatment is likely having a positive effect. However, if those levels remain unaffected or continue to rise, the therapy may not be working.
Unfortunately, the general ALS patient population has yet to benefit from a drug therapy that has shown powerful efficacy. However, there are genetic forms of ALS where drugs have been shown to reduce neurofilament light levels and, with some delay, stop disease progression. Using this NfL analysis, clinicians may be able to determine individual ALS patients’ responses to treatment.
As of March 2025, Mayo Clinic launched a study on an experimental ALS drug therapy, called MN-166 (ibudilast), after receiving a $22 million grant from the NIH. The study is through the federal government’s Accelerating Access to Critical Therapies for ALS Act, and it will give hundreds of patients access to the drug.
The primary marker for this drug’s efficacy will be via concentrations of NfL in plasma, using the NFLP assay. Dr. Oskarsson is leading the study, which will not require a placebo arm. “This is an open-label study, or an expanded access program with a study attached to it, so to speak,” he says. “So we will be able to look at the data as we go and follow these NfL numbers. We will measure the NfL levels and other functional measures every three months and compare these to the patients’ baseline values.”
Eoin Flanagan, M.B., B.Ch., chair of the Division of MS and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota, also uses the NFLP assay as an adjunct tool in his patient practice.
“Neurofilament light chain can serve as a good biomarker when the MS is active or more inflamed,” says Dr. Flanagan. “We usually use MRI to look for disease activity, but this assay is an additional parameter. We're using it to guide what the risk is in the future for this patient — how frequently do we need to see them? How frequently do we need to do their MRIs? What does the future look like for that patient?
“It can also help guide our treatment decisions. If those neurofilament levels are high, then we can get them on a stronger treatment and then monitor those levels as we go forward. If it starts to elevate, even if the MRI is normal, it gives us another way of detecting that. And if it stays low, then things are going well.”
Other diagnostic tools Dr. Flanagan uses include wearable technology with which to measure a patient’s gait. “So they're wearing these materials and we can then match neurofilament light chain levels with these measures of how they’re walking,” he says.
“We're trying to innovate more sophisticated ways of measuring how patients are doing because traditional measures — using our neurologic examination and MRIs — might only tell part of the story,” says Dr. Flanagan. “So having this neurofilament light chain assay and then matching it to some other parameters can really help us get an overall picture and see what's happening beneath the surface that we may not be able to see otherwise.”
As patient care becomes more and more individualized, Dr. Oskarsson is already using the NFLP assay to help assess new therapies for patients with ALS who have rarer forms of the disease. For example, he is conducting a study on a patient whose ALS was caused by a mutation in the CHCHD10 gene. The patient was put on a personalized antisense oligonucleotide (ASO) therapy drug designed by the n-Lorem Foundation. During a series of doses over the trial period, the patient’s Nfl levels were repeatedly measured as the primary efficacy marker for the drug.
At first, the patient experienced a slowing of symptom progression, but he has now noted improved leg strength (e.g., with a leg press increase from 80 to 120 lbs.). “Our approach has knocked down the patient’s neurofilament levels by 50%, and his disease has not progressed now, as of last June to the present,” says Dr. Oskarsson.
Further, the new study just launched on ibudilast therapy will offer important new data on the assay’s potential use in individualized care. “The assay can serve as a marker of the disease rate and efficacy of a drug,” says Dr. Oskarsson. “And we'll be able to look at that on an individual basis. Again, is ibudilast shifting someone's neurofilament up or down?”
The NFLP assay is also playing a role in MS trials. “There's some recent work showing that the Epstein-Barr virus is associated with risk of MS,” says Dr. Flanagan. “Some of the studies proved that the infection is a trigger for multiple sclerosis and were able to show that some of those patients who developed MS also had higher neurofilament light chains.”
Dr. Flanagan envisions the potential for NfL levels to be an early predictor of MS. “Sometimes, even before the diagnosis of MS is made, those neurofilament levels may be up,” he says. “So it may be an opportunity for us to get an earlier diagnosis. You can imagine, for example, in patients who have family members with MS, if they wanted to be screened, you could potentially use that blood test to look and see if these levels are elevated, and then that might be somebody you want to do an MRI on.
“So I think there's going to be more and more studies in the future trying to get the diagnosis earlier. Because the treatments we have for MS now, they're very, very effective. We can really shut down the inflammatory activity. The earlier we can get in with treatment, the better. So this assay might serve as a way to get an earlier diagnosis for patients in the future, too.”
In the future, the assay’s role as a diagnostic tool could also expand into other neurological diseases, and beyond. “A number of neuropathological things can kind of elevate neurofilament levels,” says Dr. Bornhorst. “NfL may end up being a neurological tool analogous to the widespread use of troponin to indicate cardiac AMI (acute myocardial infarction). Elevated NfL concentrations may mean a person has a transient inflammation or neurological insult. These levels are also elevated in a concussion, and or TBI (traumatic brain injury). There’s a lot of other potential uses for this assay, and we’re still exploring those. It’s a very broad, fast-moving field.”
