NEUROFILAMENT LIGHT CHAIN, AN EARLY BIOMARKER FOR POLYNEUROPATHY IN HEREDITARY ATTR AMYLOIDOSIS.

BackgroundSerum neurofilament light chain (sNfL) is a sensitive marker for polyneuropathy (PNP) in hereditary transthyretin-related (ATTRv) amyloidosis patients and correlates with the severity of polyneuropathy [1-4]. We hypothesized that sNfL may diagnose neuronal damage in patients with hATTR amyloidosis before the onset of symptoms and before PNP can be detected by electromyography (EMG) examination.ObjectivesTo establish the course of sNfL in three different groups: 1. persistently asymptomatic variant carriers (with and without detected amyloid), 2. ATTRv amyloidosis patients with PNP on treatment, 3. variant carriers who develop PNP.MethodssNfL levels were assessed longitudinally in asymptomatic variant carriers (with and without detectable amyloid), ATTRv amyloidosis patients with PNP on treatment (either a transthyretin (TTR) stabilizer or patisiran, an RNA interference therapeutic), and variant carriers who developed PNP. PNP was established by EMG examination. The single-molecule array (Simoa) assay was used to assess sNfL levels.ResultssNfL levels significantly increased over 1 year in 20 persistently asymptomatic carriers (p<0.001), with the strongest increase in variant carriers (n=8) with detectable amyloid in the subcutaneous abdominal fat tissue. In 21 symptomatic ATTRv amyloidosis patient with PNP on treatment with a TTR stabilizer, sNfL levels remained stable over 1 year. In 24 patients treated with patisiran, sNfL levels significantly decreased after 1 year of treatment (p=0.01). In 8 out of 9 variant carriers who developed PNP a rise in the sNfL level could be observed before the onset of symptoms and establishment of PNP by EMG examination (Figure 1).Figure 1.ConclusionsNfL is a marker for early neuronal damage since a rise in sNfL level occurs before abnormalities can be detected by EMG examination. Our data support the use of sNfL in monitoring disease progression, screening asymptomatic variant carriers and monitoring of treatment effect.References[1]Louwsma et al. Amyloid 2021;28(1):50-55[2]Maia et al. Amyloid 2020;27(2):97-102[3]Kapoor et al. J Perpher nerv syst 2019;24:314-319[4]Ticau et al. Neurology 2021;96:e412-e422Disclosure of InterestsAnne Floor Brunger: None declared, Milou Berends: None declared, Johan Bijzet: None declared, Paul van der Zwaag: None declared, Bart-Jan Kroesen: None declared, Charlotte Teunissen: None declared, Sjors in ‘t Veld: None declared, Gea Drost: None declared, Fiete Lange: None declared, Reinold Gans: None declared, Bouke Hazenberg Consultant of: Alnylam and Pfizer, Hans L.A. Nienhuis Consultant of: Alnylam and Pfizer