Potential biomarkers for disease severity in Charcot Marie-Tooth disease: a comparative study of NFL, GFAP, FGF-21, and GDF-15 concentrations

Objectives. Charcot-Marie-Tooth disease (CMT) is the most prevalent inherited
neuropathy, it is currently lacking molecular markers for evaluating disease progression. However, there is promise in the potential use of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and fibroblast growth factor 21 (FGF-21) as biomarkers for assessing nerve damage, but growth differentiation factor 15 (GDF-15) has been proposed as a biomarker for muscle mass reduction in CMT. The study aimed to compare NfL, GFAP, FGF-21, GDF-15 concentrations between a control group and a CMT group, examining their correlation with
disease severity, to assess the reliability of these biomarkers for future research.
Materials and methods. 43 CMT patients and 43 healthy controls were enrolled in the study. Disease severity was assessed using CMT Neuropathy Score version 2 (CMTNSv2). Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with single molecule array (Simoa), fibroblast growth factor 21 (FGF-21), and growth differentiation factor 15 (GDF-15) with an enzyme-linked immunosorbent assay.
Results. The GDF15, FGF21, NfL and GFAP concentrations were significantly higher in the CMT patient group than in the controls (p<0,05). The GDF15 concentration had a statistically significant correlation with patients age and NfL level (rs=0.57, p<0.001; rs=0.34, p<0.027;), NfL and GFAP correlated with the CMTNSv2 (rs=0.46, p=0.002; rs=0.31, p=0.04).
Conclusions. Our study has provided confirmation that plasma concentrations of NfL, GFAP, GDF15, and FGF21 are significantly elevated in CMT patients compared to controls. Moreover, NfL and GFAP levels were correlated with the clinical severity of CMT. These findings suggest that NfL and GFAP can be reliable disease indicators in future research.