Plasma neurofilament light chain concentration in the inherited peripheral neuropathies

Abstract

ObjectiveTo perform a cross-sectional study to determine whether plasma neurofilament light chain (NfL) concentration is elevated in patients with Charcot-Marie-Tooth disease (CMT) and if it correlates with disease severity.MethodsBlood samples were collected from 75 patients with CMT and 67 age-matched healthy controls over a 1-year period. Disease severity was measured using the Rasch modified CMT Examination and neuropathy scores. Plasma NfL concentration was measured using an in-house-developed Simoa assay.ResultsPlasma NfL concentration was significantly higher in patients with CMT (median 26.0 pg/mL) compared to healthy controls (median 14.6 pg/mL, p < 0.0001) and correlated with disease severity as measured using the Rasch modified CMT examination (r = 0.43, p < 0.0001) and neuropathy (r = 0.37, p = 0.044) scores. Concentrations were also significantly higher when subdividing patients by genetic subtype (CMT1A, SPTLC1, and GJB1) or into demyelinating or axonal forms compared to healthy controls.ConclusionThere are currently no validated blood biomarkers for peripheral neuropathy. The significantly raised plasma NfL concentration in patients with CMT and its correlation with disease severity suggest that plasma NfL holds promise as a biomarker of disease activity, not only for inherited neuropathies but for peripheral neuropathy in general.

Peripheral nervous system involvement in lymphomas

“…Hopefully, in the nearby future, new diagnostic tools may become available. Recently, attention has been paid to neurofilament light chain as potential marker of peripheral nerve damage both in the preclinical and clinical setting . A possible diagnostic and prognostic role of neurofilaments in the polyneuropathies workup is currently under investigation.…”

Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies

“…57 NEFL assays in CMT has provided an important marker of axonal degeneration in CMT1A, 9 but there is currently a lack of biomarkers to assess disease processes in the SCs that are most directly affected by the PMP22 gene duplication. Biomarkers can be used to not only measure disease process (NEFL levels) and disease burden (MRI), but also target engagement for a given therapy.…”

“…2 A recent study using antisense oligonucleotides showed dramatic improvement in a severe mouse model of CMT1A as well as a more mild rat model of the disease. 7,8 In addition, neurofilament L protein (NEFL) levels are elevated in CMT1A plasma samples and correlate with severity as measured by the CMTNS-R and CMTES-R. 9 Given that several candidate therapeutic strategies are aimed to reduce PMP22 mRNA levels, 3,10 developing a robust method for establishing PMP22 mRNA levels from skin biopsies would be a valuable marker of target engagement for clinical trials in CMT1A. 4 Clinical outcome assessments, such as the Rasch modified CMT Neuropathy or Exam Scores (CMTNS-R/ CMTES-R), measure severity of neuropathy in adults and children with CMT1A.…”

Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis

“…Following axonal damage, neurofilaments are released into the circulation and can be detected in the plasma using highly sensitive analytical methods such as the Single molecule array (Simoa) platform . We have previously shown that pNFL is raised in patients with Charcot‐Marie‐Tooth (CMT) disease and that it correlates with disease severity . In this study, we sought to determine whether pNFL was also raised in patients with ATTRm neuropathy compared to controls and if it correlates with disease severity and neuropathy scores.…”