Examining the Correlation Between Neurofilament Levels and Clinical Features in a Friedreich Ataxia Cohort from the Czech Republic

Abstract

Objective: Friedreich's ataxia (FA) is the most common autosomal recessive hereditary ataxia caused by a mutation in the FXNgene characterized by ataxia, dorsal root syndrome, scoliosis, cardiomyopathy, and other symptoms. Neurofilaments, structuralproteins which play a key role in the maintenance of axonal caliber and axonal integrity, may be an interesting biomarker ofneurodegeneration in FA. To better understand the role of neurofilaments in the pathogenesis of FA, we conducted a study toexamine the relationship between phosphorylated neurofilament heavy chain (pNFH) and neurofilament light chain (NFL) andclinical features in a well-characterized FA patient cohort.Methods: In the Center of Hereditary Ataxias in Prague were recruited 40 FA patients (mean age 33, range 8-72, 6 of them agebellow 18) between August 2021 and June 2022 and underwent clinical assessment using the European Friedreich's AtaxiaConsortium for Translational Studies (EFACTS) protocol at the baseline (T0) and in one year follow-up (T1) on the same day thatblood samples were collected and frozen. The blood samples for gene testing were collected at T0. Blood samples from 14 agematched healthy controls (HC) served as a reference (mean age 34). Plasma pNFH levels were measured by an enzyme-linkedimmunosorbent assay, ELISA.Results: Preliminary results from the T0 examination showed higher levels of pNFH (mean 48 pg/ml, range 9-202) in FA patientscompared to HC (mean 15 pg/ml, range 10-18). Patients with a faster average progression of ataxia according to the scale for theassessment and rating of ataxia (SARA) had higher levels of pNFH, while patients with higher mobility impairment had lower pNFHlevels. Both patients with better performance on the functional 9-hole peg test and patients with a younger age at initialexamination had higher levels of pNFH.Conclusions: Current literature and our preliminary results suggest that neurofilament levels in FA patients are significantlyincreased compared to HC and in the early stages of the disease. They gradually decrease with increasing age and more severedisability and faster progression. After the T1 assessments in April 2023 are completed, we will have the opportunity to comparelevels of pNFH (ELISA) and NFL (measured by a single molecule array, SIMOA) at both T0 and T1 and examine the correlationsbetween these biomarker levels and clinical data at both time points.