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 FXN gene characterized by ataxia, dorsal root syndrome, scoliosis, cardiomyopathy, and other symptoms. Neurofilaments, structural proteins which play a key role in the maintenance of axonal caliber and axonal integrity, may be an interesting biomarker of neurodegeneration in FA. To better understand the role of neurofilaments in the pathogenesis of FA, we conducted a study to examine the relationship between phosphorylated neurofilament heavy chain (pNFH) and neurofilament light chain (NFL) and clinical 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 age bellow 18) between August 2021 and June 2022 and underwent clinical assessment using the European Friedreich's Ataxia
Consortium for Translational Studies (EFACTS) protocol at the baseline (T0) and in one year follow-up (T1) on the same day that blood samples were collected and frozen. The blood samples for gene testing were collected at T0. Blood samples from 14 age matched healthy controls (HC) served as a reference (mean age 34). Plasma pNFH levels were measured by an enzyme-linked immunosorbent assay, ELISA.
Results: Preliminary results from the T0 examination showed higher levels of pNFH (mean 48 pg/ml, range 9-202) in FA patients compared to HC (mean 15 pg/ml, range 10-18). Patients with a faster average progression of ataxia according to the scale for the assessment and rating of ataxia (SARA) had higher levels of pNFH, while patients with higher mobility impairment had lower pNFH levels. Both patients with better performance on the functional 9-hole peg test and patients with a younger age at initial examination had higher levels of pNFH.
Conclusions: Current literature and our preliminary results suggest that neurofilament levels in FA patients are significantly increased compared to HC and in the early stages of the disease. They gradually decrease with increasing age and more severe disability and faster progression. After the T1 assessments in April 2023 are completed, we will have the opportunity to compare levels of pNFH (ELISA) and NFL (measured by a single molecule array, SIMOA) at both T0 and T1 and examine the correlations between these biomarker levels and clinical data at both time points.