Trend in blood serum levels of light and heavy chains of neurofilaments in infants with spinal muscular atrophy against background of the use of gene therapy

Introduction. Determination of neurofilaments (NF) levels in blood serum and CSF in children with spinal muscular atrophy (SMA) may be a promising biomarker of the severity and course of the disease, as well as a way of assessing the effectiveness of pathogenetic therapy. The aim of the study was to determine the blood serum NF levels of in 0–24 months infants with SMA type I at the presymptomatic stage of the disease before and after gene therapy with onasemnogene abeparvovec (OA). Materials and methods. The study included one hundred fifty five 0–24 months infants including 76 neurologically healthy children (group II), as well as 79 patients with SMA from group I (subgroup Ia — 44 infants with SMA type I, Ib — 35 infants at the presymptomatic stage of the disease) with a diagnosis of SMA. The majority of infants with type I SMA (subgroup Ia) had 2 copies of the SMN2 gene (n = 43; 97.7%), while infants from subgroup Ib (asymptomatic patients) had 3 copies (n = 31; 88.6%). Results. The values of NF light and heavy chains in infants from group I were obtained before and after 3–6, 7–12, and 13–24 months after gene therapy with OA. The NF light chains level in the Ia subgroup before treatment was significantly higher than in the Ib subgroup (p < 0.001) and higher than in the control group (p < 0.001). The serum level of NF heavy chains in the Ia subgroup before treatment was also significantly higher than in the control group. In the Ia subgroup, there was a significant decrease (p < 0.01) in serum NF light chains 3–6 months after gene therapy (Me [Q1; Q3] — 22.97 [6.00; 48.54]) compared with the same indices before treatment (6.0 [5.92; 7.78]). Subsequently, after 7–12 months (6.15 [5.15; 7.30]) and 13–24 months (6.0 [5.7; 6.6]), stabilization of Me values was noted with a decrease in interquartile ranges. In the Ib subgroup, there was also a significant decrease (p < 0.01) in serum NF light chains levels 3–6 months after OA gene therapy (6.0 [6.00; 7.25]) compared with these indices before treatment (6.0 [6.00; 31.43]). Conclusion. Determination of the blood serum NF light and heavy chains levels in SMA patient before and after gene therapy can be regarded as a marker of the severity of the disease and the effectiveness of treatment.