A recently published study in the Journal of the Peripheral Nervous System demonstrates that serum neurofilament light chain (sNfL) may be a reliable and promising biomarker of peripheral neuropathy in hereditary transthyretin-related (hATTR) amyloidosis

The research team recruited patients from October 2019 to July 2021 from the neuromuscular department of the Lausanne University Hospital in Switzerland. To be included in the study, patients had to be aged at least 18 years and carry a specific type of genetic transthyretin (TTR) mutation; they could be symptomatic or asymptomatic. 

“To our knowledge, this is the first prospective study to have assessed sNfL levels, in a one-year follow-up, in patients with hATTR amyloidosis who have undergone a comprehensive and thorough clinical (with measurement of several functional scores) and electrophysiological evaluation,” the authors noted.

Study results reported significantly higher sNfL levels (about 3.6-fold) in the symptomatic hATTR patients compared to asymptomatic ones. Moreover, a significant difference was observed in the sNfL levels of symptomatic hATTR patients to those with a healthy control cohort, with a median Z score of 2.52. These results suggested a correlation between the elevation of sNfL level and symptom onset. 

Results also showed an association between sNfL level reduction (mean reduction -21.9 pg/mL) and the introduction of gene silencing therapy with patisiran in 2 patients. Furthermore, the increase in sNfL level was not significant during the 1-year follow-up, as the researchers were not able to investigate any patient who considerably worsened, nor any asymptomatic patient who became symptomatic.

Read more about hereditary transthyretin amyloidosis therapies

hATTR amyloidosis, a rare genetic disorder with recessive, dominant transmission, is caused by a point mutation in the TTR gene. Typical disease characteristics include debilitated and potentially life-threatening axonal length-dependent polyneuropathy.

Neurofilament light chain (NfL), a protein typically found in the cytoskeleton of nerve cells, is released into the extracellular space when nerve cells are damaged. Multiple recent studies have reported increased sNfL in patients with hATTR amyloidosis and polyneuropathy and its correlation with disease severity.

“In this prospective study, we showed that it can reliably distinguish between asymptomatic and symptomatic patients and is well correlated with peripheral neuropathy severity, as measured with functional and electrophysiological scores,” the authors added. “In conclusion, sNfL is a promising biomarker of peripheral neuropathy in hATTR amyloidosis.”

The authors could not confirm if the increase in sNfl levels preceded the onset of neuropathy, though recent data in the literature suggest this. “Larger scale studies with longer longitudinal follow-up are needed to confirm our data,” they concluded.

Reference

Loser V, Benkert P, Vicino A, et al. Serum neurofilament light chain as a reliable biomarker of hereditary transthyretin-related amyloidosis-A Swiss reference center experienceJ Peripher Nerv Syst. Published online December 5, 2022. doi:10.1111/jns.12524