Trend in parameters of motor nerve conduction against the background of gene therapy in early age patients with spinal muscular atrophy

Introduction. In children with spinal muscular atrophy (SMA), reliable indicators (biomarkers) are needed to predict the disease, which could reflect the underlying process of the disease. It is believed that the parameters of motor nerve conduction studies (MNCV) (amplitude and area of the compound muscle action potential (CMAP), the motor unit number estimation) may correlate with the degree of denervation in SMA and with the severity of motor disorders.

The purpose of the study. To detect the trend in MNCV parameters in SMA type I patients with clinical manifestations of the disease and children at the presymptomatic stage of the disease, against the background of treatment with onasemnogen abeparvovek.

Materials and methods. The study included sixty eight SMA children, including 42 boys (53.2%). All children received gene therapy with the onasemnogen abeparvovek. 33 children were treated at the presymptomatic stage (age at the time of treatment was 2.12 ± 0.91 years (95% CI 1.80–2.45), min — 1.00, max — 5.00). In 35 SMA type I children, treatment started when clinical symptoms of the disease were already present (age at the time of treatment was 3.40 ± 1.85 years (95% CI 3.10–4.25), min — 1.00, max — 7.00). All children included in this study underwent MNCV before the start of therapy and for the next 2 years. The amplitude of the negative peak of the CMAP from the abductor digiti minimi muscle during stimulation of the ulnar nerve and nerve conduction velocity (NCV) along the distal part of the ulnar nerve were determined. Due to the fact that the values of most of the MNCV parameters did not obey the normal distribution, they were described using the values of the median (Me) and the lower and upper quartiles (Q1–Q3), minimum (min) and maximum (max).

Results. In the cohort of presymptomatic patients, the CMAP and NCV parameters did not significantly differ from the normative data before the start of therapy, and against the background of treatment with onasemnogen abeparvovek, an increase in the CMAP and NCV amplitude of the was noted with increasing age in patients. The amplitude of the CMAP and NCV before treatment were 5.00 mV (4.30–5.30), min — 1.40, max — 8.00 and 33.60 m/s (32.40–38.10), min — 27.40, max — 48.90, and at the age of 13 to 24 months — 6.25 mV (5.20–6.85), min — 4.70, max — 7.80 and 55.20 m/s (52.80–57.60), min — 49.10, max — 60.30, respectively. All SMA type I patients showed a significant decrease in the amplitude of the M-response both before therapy and during 2-year follow-up after the start of treatment. The amplitude of the CMAP and NCV before treatment were 0.28 mV (0.13–0.65), min — 0.05, max — 2.20 and 31.90 m/s (27.50–35.90), min — 22.30, max — 52.00, and at the age of 13 to 24 months — 0.70 mV (0.46–1.15), min — 0.17, max — 4.60 and 48.40 m/s (43.95–50.98), min — 38.90, max — 56.10, respectively.

Conclusion. When comparing the MNCV parameters in presymptomatic with SMA type I patients, significant differences were shown, which were manifested in symptomatic patients with a low amplitude of the CMAP and reduced values of NCV both before therapy and during 2-year follow-up after treatment with onasemnogen abeparvovek. Thus, conducting MNCV in children with SMA is an easily feasible study, and evaluating the amplitude of the CMAP makes it possible to reliably, albeit indirectly, verify degeneration of spinal cord motor neurons in symptomatic patients against the background of pathogenetic treatment.

Compliance with ethical standards. Permission was obtained from the local ethics committee of the National Medical Research Center for Children’s Health to conduct this study Minutes of the meeting of the local ethics committee from October 06, 2022, No. 10.

Contribution:
Fisenko D.A. — concept and design of the review, writing the text, editing;
Kurenkov A.L. — concept and design of the review, writing the text, editing;
Kuzenkova L.M. — concept and design of the review, editing;
Chernikov V.V. — statistical data processing;
Uvakina E.V. — concept and design of the review, editing;
Popovich S.G. — editing;
Bursagova B.I. — editing;
Belousova T.N. — editing;
Kniazeva N.Y. — editing;
Novikov M.Y. — editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: November 14, 2024
Accepted: November 29, 2024
Published: January 31, 2025

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