Neurofilament Light Chain may Serve As a Biomarker of Neuropathy in Hattr Amyloidosis with Cardiomyopathy

Abstract

Introduction Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease due to deposition of transthyretin (TTR) amyloid in various organs and tissues. Historically the disease has been described by predominant clinical manifestation of cardiomyopathy (CM) or polyneuropathy (PN), however a majority of patients are known to develop a mixed phenotype. Because of this, PN symptoms may not always be assessed in patients with predominant CM and neuropathy progression may continue. The potential of neurofilament light chain (NfL) as a non-invasive biomarker of nerve damage in patients with hATTR amyloidosis with PN has previously been described; however to date no studies have investigated NfL in patients with predominant CM. Hypothesis NfL may serve as a biomarker of co-existing neuropathy in patients with hATTR amyloidosis with predominant CM and could lead to early detection and treatment of nerve damage, thus improving patient care. Methods Plasma NfL levels were measured in baseline samples from patients with hATTR amyloidosis with CM from the Phase 3 ENDEAVOUR study (n = 194; V122I variant = 111) and compared with NfL levels from healthy controls (n = 53) and baseline samples from patients with hATTR amyloidosis with PN from the Phase 3 APOLLO study (n = 193). Polyneuropathy Disability (PND) score was also taken into account for NfL analyses. Results Elevated plasma NfL levels were observed in patients with hATTR amyloidosis with CM relative to healthy controls (54.1 pg/mL vs 16.3 pg/mL, p 0 (n = 101; evidence of neurological impairment) were not significantly different to those in patients with hATTR amyloidosis with PN (p = 0.15), where all patients had a PND>0. Patients with hATTR amyloidosis with CM and the V122I variant, generally considered to cause a predominant CM phenotype, also had elevated plasma NfL levels relative to healthy controls (44.9 pg/mL vs 16.3 pg/mL, p Conclusions NfL may serve as a biomarker of nerve damage in patients with hATTR amyloidosis, regardless of the predominant manifestation. This analysis also suggests PN may be underdiagnosed in patients with predominant CM, such as those with a V122I variant, and NfL may be a useful biomarker to support earlier diagnosis of PN in these patients.