Neurofilament Light Chain Levels Able Blood Marker of Likely ALS Progression, Study Finds
People with amyotrophic lateral sclerosis (ALS) have higher blood serum levels of neurofilament light chain (sNfL) than do healthy people, a new study found. Its work also further supported sNfL’s usefulness as a marker of likely disease progression and outcomes, with higher concentrations indicating poorer survival.
High neurofilament light chain levels have been proposed as markers of degeneration in neurological conditions such as ALS and multiple sclerosis. However, prior studies in ALS have been limited by the relatively low sensitivity of the techniques used to detect these molecules in the blood.
Quanterix’s ultra-sensitive Simoa assay has enabled more accurate and reproducible measures of extremely low sNfL levels. These levels correlate with the amount of this nerve cell-derived component in the cerebrospinal fluid, the liquid surrounding the brain and spinal cord. But how sNfL levels might relate to ALS prognosis, a patient’s likely progression, remains unclear.
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Investigators at an ALS center in Montpellier, France, addressed this gap using what they called “the largest series of sNfL levels by Simoa in ALS patients.” They also compared sNfL to other known prognostic factors for the disease. In total, they analyzed serum samples taken from 198 patients at diagnosis (118 men) and from 21 age-matched healthy people serving as controls.
Patients’ mean age was 65.4 years, their symptom duration was 14.5 months, and their mean weight loss was 4.5 kg (about 10 lbs). Most (180) had sporadic disease, while 18 had familial ALS; the site of disease onset was spinal in 136 cases and bulbar in 62 (bulbar refers to first manifestations affecting speech and swallowing).
Results revealed significantly higher sNfL levels in patients than in controls. A lever higher than 15.0 pg/mL could differentiate between the two groups with a sensitivity of 94% and a specificity of 100%.
Within the ALS group, women had significantly higher sNfL levels than men, while patients with shorter disease duration had higher levels than those with a longer span of time from symptom onset to diagnosis. Patients with bulbar onset also had higher sNfL levels than those with spinal onset. No notable differences were seen between sporadic and familial cases.
Seventy-eight patients (39.4%) died over a median follow-up of 27 months. Tests showed that those with sNfL levels of 71.2 pg/mL or higher were at greater risk of death.
Six other factors analyzed at a first visit also predicted mortality: age at disease onset, site of onset, ALS Functional Rating Scale revised (ALSFRS-R) score, weight loss, and lung function measures like forced vital capacity (FVC) and maximum inspiratory pressure.
Specifically, an increase of 1 pg/mL in sNfL levels over the 27 months corresponded to a 0.74% greater risk of death, a weight loss of 1 kg (2.2 lbs) was associated with a 4.9% increase in such risk, and bulbar onset corresponded to a 68% greater risk compared to spinal onset.
A subsequent analysis showed that sNfL levels, degree of weight loss, and site at onset were independent predictors of mortality. In turn, both sNfL and FVC were independent predictors in 139 patients with complete data regarding lung health. In a subgroup of 142 patients, higher sNfL serum levels correlated with a greater likelihood of decline in ALSFRS-R scores during follow-up, “an important clinical parameter [that] correlated with prognosis,” the team said.
“Compared to all other factors influencing survival, sNfL concentration was the parameter most correlated to ALS survival,” the scientists wrote.
“Taken together with other studies,” they added, “our data show that sNfL levels may be measured early in ALS patients not only to help ascertaining diagnosis but also to better determine prognosis and to refine outcome measures in clinical trials.” The Simoa assay also requires only a blood sample, enabling its use in routine clinical settings.
As all patients in this study started on Rilutek (riluzole, by Sanofi) after their diagnosis, studying the effects of treatment on sNfL levels would be important in future studies, the researchers said.