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Higher blood levels of neurofilament light chain (sNfL) were linked with disability, brain atrophy, and other features of multiple sclerosis (MS) in an ongoing and real-world study, reinforcing its potential as a new biomarker of MS progression.
The results of the study, “Associations of Serum Neurofilament Light Chain with Clinical and Radiological Measures in a Large Real World MS Population,” were presented at the virtual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, by Elias Sotirchos, MD, with Johns Hopkins University.
Neurofilaments are structural proteins found in nerve cells that primarily act to support the cytoskeleton — a network of diverse proteins that give cells their shape and stability. They are composed of a light chain subunit and either a medium or heavy chain subunit.
Nerve cells release these structural proteins into circulation following injury. Higher-than-normal levels of sNfL in the blood, or serum, are associated with MS and other neurological disorders, and are being investigated as a possible biomarker.
“In MS, there is ample evidence that serum neurofilament light chain levels are associated with clinical radiological measures of inflammatory disease activity, are predictive of future disability worsening, and [of] brain and spinal cord atrophy, and are modulated by disease-modifying therapies (DMTs),” Sotirchos said.
Few studies, however, have evaluated sNfL changes in large, real-world MS populations.
To get a clearer picture of sNfL’s clinical value as an MS biomarker, an international team of researchers investigated how it associates with patients’ differing demographics, the presence of other medical conditions (comorbidities), and clinical and radiological characteristics.
They measured sNfL levels in 6,968 MS patients and 201 healthy people (control group) through a combination of clinical and imaging data, as well as biological samples collected during routine visits. Patient information came from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a Biogen-sponsored network of healthcare institutions in the United States and Europe.
Females accounted for close to three-quarters of both the MS and control populations (72% and 74%, respectively), and close to one-fifth of each group was non-white.
MS PATHS “provides a unique opportunity for clinical validation of sNfL as a biomarker of MS in a large, ‘real-world,’ well-characterized, prospective cohort,” Sotirchos said. “A strength of this cohort was the large proportion of non-White participants, at about 20%.”
Among patients, about 62% had relapsing-remitting MS, a mean age of 48, and a median MS duration of 13 years. Their disability level was considered mild.
Higher-than-usual sNfL levels — measured using an immunoassay by Siemens Healthineers — were found in 1,202 MS patients, or 17.2% of the study group. These elevated levels correlated with progressive MS, non-white race, having diabetes, and smoking.
“We observed that individuals with diabetes had significantly increased odds of elevated sNFL, compared to non-diabetics,” Sotirchos said.
Investigators also found that current and former smokers had higher odds of elevated sNFL levels compared with patients who had never smoked tobacco.
An individual’s age and disease duration showed complex relationships with sNfL concentration. But higher sNfL levels tended to be found more frequently in younger patients (18 to 38 years old) with shorter disease duration (up to six years).
A higher body mass index (a ratio of a person’s weight to height), in turn, correlated with a lesser likelihood of higher sNfL levels.
Elevated sNfL was tied to poorer neurological function, as measured in tests of walking speed, manual dexterity, and mental processing speed. Higher sNfL levels were also linked to greater brain atrophy, a lower volume for the thalamus (a brain region associated with cognitive and sensorimotor functions), and higher lesion volume.
Follow-up is continuing with this MS patient group, Sotirchos said, as is work to expand on data collected from healthy controls “to allow more precise determination of reference ranges.”
One key study benefit, he added, will be in refining measurements needed to better conduct future sNFL studies.
“Based on our results,” Sotirchos said, “it appears that reference ranges may need to account for sex, race, body mass index, and comorbid/lifestyle factors in order to potentially improve the performance of sNfL as a biomarker in MS and other neurological diseases.”
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