Nerve damage marker tied to hATTR-PN symptom severity in new study

Increased levels of neurofilament light chain (NfL), a marker of nerve damage, are associated with more severe neurological symptoms in people with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), according to a new study from Brazil.

Results also indicated that tafamidis meglumine, the only hATTR-PN therapy covered by Brazil’s public health system, was associated with lower levels of this nerve damage marker. Pfizer’s tafamidis meglumine is approved in Brazil and several other countries outside the U.S. under the brand name Vyndaqel.

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NfL may help track hATTR-PN severity

Blood NfL “emerges as a promising biomarker for assessing disease severity, progression, and treatment response in [hATTR-PN],” the researchers wrote.

The study, “Correlation between neuropathy severity and neurofilament light chain levels in Brazilian patients with hereditary transthyretin amyloidosis,” was published in Scientific Reports.

hATTR-PN, also known as familial amyloid polyneuropathy (FAP), is a progressive disease caused by mutations in TTR, the gene that encodes the protein transthyretin. The mutated protein forms toxic clumps, or amyloid deposits, that can cause neuropathy, or peripheral nerve damage, ultimately driving neurological symptoms.

“Despite advances in disease-modifying therapies, including the availability of Tafamidis, delayed diagnosis remains a major challenge, contributing to increased [illness] and mortality,” the researchers wrote. “Therefore, the identification of reliable biomarkers for early detection, disease staging, and therapeutic monitoring is essential.”

NfL is a structural protein normally found in nerve fibers. When nerves become damaged, this protein can leak into the blood and other bodily fluids; as such, elevated NfL levels in blood are a marker of nerve damage.

Previous studies have shown that higher-than-normal NfL levels in the blood may be a marker of hATTR-PN, even before symptoms have developed, and that patients with higher levels of this marker tended to have worse symptoms as measured by a standardized measure called the Neuropathy Impairment Score (NIS).

Researchers measured plasma NfL levels

Here, a team of researchers in Brazil set out to see if similar patterns were evident in a group of 20 people carrying disease-causing TTR mutations at their center. Twelve of them were already experiencing symptoms (symptomatic), while the remaining eight weren’t (asymptomatic). All but two patients carried Val30Met, the most common hATTR-PN-causing mutation.

Nine of the symptomatic patients were on tafamidis meglumine, an oral therapy that stabilizes transthyretin to help prevent toxic clumps from forming and slow disease progression.

The study also included nine healthy volunteers, who were used as controls.

Results showed that median blood NfL levels were generally lower in healthy controls (5.21 picograms/mL) than in asymptomatic patients (13.95 picograms/mL), but this difference was not statistically significant.

“These findings suggest that perhaps in a larger [group of patients], NfL could detect early subclinical [nerve] damage prior to the onset of clinical symptoms, supporting its potential as a sensitive early biomarker of neurological involvement in [hATTR-PN],” the researchers wrote.

Symptomatic patients taking tafamidis meglumine had higher median blood NfL levels (34.8 picograms/mL) than healthy controls and asymptomatic patients. This difference reached statistical significance compared with healthy controls.

This suggests that “early therapeutic intervention may attenuate or slow neuronal damage, reinforcing the importance of timely diagnosis and treatment initiation,” the team wrote.

Untreated symptomatic patients had highest NfL levels

The three symptomatic patients who were not on the therapy had even higher median blood NfL levels (134.8 picograms/mL). While these were significantly elevated relative to healthy people, differences seen compared with asymptomatic and treated symptomatic patients did not reach statistical significance. Again, the small sample size may have limited statistical power.

“This study suggests that [blood NfL] may serve as a useful biomarker for assessing disease severity and progression in Brazilian patients with [hATTR-PN],” the researchers wrote. “Differences in [blood] NfL levels were observed between symptomatic and asymptomatic individuals, as well as between treated and untreated patients, indicating a potential role in early detection and therapeutic monitoring.”

Further statistical analyses of data from symptomatic patients showed a positive correlation between higher blood NfL levels and higher NIS values, reflecting more severe neurological symptoms.

“The association between higher NfL concentrations and greater neuropathy severity points to its possible involvement in tracking disease evolution,” the team wrote.

“While our results support [blood] NfL as a sensitive biomarker of neurological involvement and disease stage in [hATTR-PN], longitudinal studies with pre-treatment [initial] measurements and stage-matched patient groups are required to clarify the specific impact of Tafamidis on NfL dynamics over time,” they concluded.