neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2025-6-1-26-36usswznneurojour-166Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSДинамика уровней лёгких и тяжёлых цепей нейрофиламентов в сыворотке крови детей со спинальной мышечной атрофией на фоне применения генной терапииTrend in blood serum levels of light and heavy chains of neurofilaments in infants with spinal muscular atrophy against background of the use of gene therapyhttps://orcid.org/0000-0002-7893-1863ФисенкоДарья АндреевнаFisenkoDaria A.

Аспирант, врач-невролог, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия 119991, Москва

e-mail: fisenko.daria@mail.ru

Postgraduate student, neurologist of the Center of child psychoneurology, National Medical Research Center of Children’s Health, Moscow, 119991, Russian Federation

e-mail: fisenko.daria@mail.ru

fisenko.daria@mail.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛюдмила МихайловнаKuzenkovaLyudmila M.

Доктор мед. наук, профессор, начальник центра детской психоневрологии, зав. отделением психоневрологии и нейрореабилитации, врач-невролог, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия; Клинический институт детского здоровья имени Н.Ф. Филатова ФГАОУ ВО «Первый МГМУ имени И.М. Сеченова» Минздрава России (Сеченовский Университет), 119435, Москва, Россия

DSc (Medicine), professor, Head of the Center for Child Neuropsychiatry, Head of the Department of Neuropsychiatry and Neurorehabilitation, neurologist, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation; N.F. Filatov Clinical Institute of Children’s Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119435, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-7269-9100КуренковАлексей ЛьвовичKurenkovAleksey L.

Доктор мед. наук, зав. лаб. нервных болезней, врач-невролог, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

DSc (Medicine), Head of the Laboratory of Nervous Diseases, neurologist, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0001-8923-4652СемикинаЕлена ЛеонидовнаSemikinaElena L.

Доктор мед. наук, зав. лабораторным отделом, гл. науч. сотр., врач лабораторной диагностики, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

DSc (Medicine), Head of the Laboratory Department, Chief Researcher, Doctor of Laboratory Diagnostics, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-8381-8793УвакинаЕвгения ВладимировнаUvakinaEugeniya V.

Канд. мед. наук, врач-невролог, ст. науч. сотр. лаб. нервных болезней, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

PhD (Medicine), neurologist, Senior Researcher of the Laboratory of Nervous Diseases, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-8750-9285ЧерниковВладислав ВладимировичChernikovVladislav V.

Канд. мед. наук, зав. отделением диагностики и восстановительного лечения, начальник методического аккредитационно-симуляционного центра, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

PhD (Medicine), Head of the Department of Diagnostics and Rehabilitation Treatment, Head of the Methodological Accreditation and Simulation Center, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-9213-5281КурбатоваОльга ВладимировнаKurbatovaOlga V.

Канд. мед. наук, ст. науч. сотр., врач клинической лабораторной диагностики, и.о. зав. лаб. экспериментальной иммунологии и вирусологии, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

PhD (Medicine), senior researcher, doctor of Clinical Laboratory Diagnostics, Acting Head of the Laboratory of Experimental Immunology and Virology, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-5444-9722КомягинаТатьяна МихайловнаKomyaginaTatiana M.

Мл. науч. сотр. лаб. экспериментальной иммунологии и вирусологии, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

Junior researcher at the Laboratory of Experimental Immunology and Virology, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0009-0004-3206-8090КоняшинМатвей ВалерьевичKonyashinMatvei V.

Врач клинической лабораторной диагностики лаб. экспериментальной иммунологии и вирусологии, ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

Doctor of Clinical Laboratory Diagnostics at the Laboratory of Experimental Immunology and Virology, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruhttps://orcid.org/0000-0002-9697-500XПоповичСофия ГеоргиевнаPopovichSofia G.

Врач-невролог, мл. науч. сотр. ФГАУ «НМИЦ здоровья детей» Минздрава России, 119991, Москва, Россия

Neurologist, junior researcher, National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation

noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center for Children’s HealthRussian FederationФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России; Клинический институт детского здоровья имени Н.Ф. Филатова ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияNational Medical Research Center for Children’s Health; N.F. Filatov Clinical Institute of Children’s Health, I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation202530042025612636Copyright © Фисенко Д.А., Кузенкова Л.М., Куренков А.Л., Семикина Е.Л., Увакина Е.В., Черников В.В., Курбатова О.В., Комягина Т.М., Коняшин М.В., Попович С.Г., 20252025Фисенко Д.А., Кузенкова Л.М., Куренков А.Л., Семикина Е.Л., Увакина Е.В., Черников В.В., Курбатова О.В., Комягина Т.М., Коняшин М.В., Попович С.Г.Fisenko D.A., Kuzenkova L.M., Kurenkov A.L., Semikina E.L., Uvakina E.V., Chernikov V.V., Kurbatova O.V., Komyagina T.M., Konyashin M.V., Popovich S.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/166Введение

Введение. Определение уровней нейрофиламентов (НФ) в сыворотке крови детей с СМА может являться биомаркером тяжести и течения заболевания, а также способом оценки эффективности проведённой патогенетической терапии.

Цель исследования — определить уровни НФ в сыворотке крови детей в возрасте 0–24 мес с СМА I типа и на пресимптоматической стадии заболевания до и после проведения генной терапии препаратом онасемноген абепарвовек (ОА).

Материалы и методы

Материалы и методы. В исследование были включены 155 детей в возрасте 0–24 мес — 76 неврологически здоровых детей (группа II), а также 79 пациентов с СМА из группы I: подгруппа Ia — 44 ребёнка с СМА I типа, Ib — 35 детей на пресимптоматической стадии заболевания. У большинства детей с подгруппы Ia (n = 43; 97,7%) было 2 копии гена SMN2, в то время как у детей подгруппы Ib (n = 31; 88,6%) — 3 копии.

Результаты

Результаты. Получены значения лёгких и тяжёлых цепей НФ у детей из группы I до и через 3–6, 7–12 и 13–24 мес после проведения генной терапии ОА. Уровень лёгких цепей НФ в подгруппе Ia до лечения был достоверно выше, чем в подгруппе Ib (p < 0,001) и в группе контроля (p < 0,001). Уровень тяжёлых цепей НФ в подгруппе Ia до лечения был достоверно выше, чем в группе контроля. В подгруппе Ia отмечено достоверное (р < 0,01) снижение уровней лёгких цепей НФ в сыворотке крови через 3–6 мес после проведения генной терапии (Me [Q1; Q3] — 22,97 [6,00; 48,54]) по сравнению с показателями до лечения (6,0 [5,92; 7,78]). Через 7–12 мес (6,15 [5,15– 7,30]) и 13–24 мес (6,0 [5,7–6,6]) отмечена стабилизация показателей медианы с уменьшением интерквартильных размахов. В подгруппе Ib также отмечено достоверное (р < 0,01) снижение уровней лёгких цепей НФ в сыворотке крови через 3–6 мес после проведения генной терапии ОА (6,0 [6,00; 7,25]) по сравнению с показателями до лечения (6,0 [6,00; 31,43]).

Заключение

Заключение. Определение уровней лёгких и тяжёлых цепей НФ в сыворотке крови у пациентов с СМА до и после проведения генной терапии ОА может расцениваться как маркер тяжести заболевания и эффективности лечения.

Соблюдение этических стандартов. На проведение данного исследования было получено разрешение локального этического комитета ФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России (протокол заседания ЛЭК № 10 от 06.10.2022).

Участие авторов

Участие авторов:Фисенко Д.А. — концепция и дизайн статьи, написание текста, редактирование;Кузенкова Л.М. — концепция и дизайн статьи, написание текста, редактирование;Куренков А.Л. — концепция и дизайн статьи, редактирование;Семикина Е.Л. — редактирование;Увакина Е.В. — концепция и дизайн статьи, написание текста, редактирование;Черников В.В. — статистическая обработка данных;Курбатова О.В. — редактирование;Комягина Т.М. — редактирование;Коняшин М.В. — редактирование;Попович С.Г. — редактирование.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Поступила 20

Поступила 20.03.2025Принята к печати 07.04.2025Опубликована 30.04.2025

Introduction

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

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

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

Conclusion. Determination of the blood serum NF light and heavy chains levels inSMA patient before and after gene therapy can be regarded as a marker of the severity of the disease and the effectiveness of treatment.

Compliance with ethical standards. Permission for conducting this study was obtained from the local ethics committee of the National Medical Research Center for Children’s Health, of the Ministry of Health of the Russian Federation (Minutes of the Local ethics committee meeting No. 10 dated 06.10.2022).

Contribution

Contribution:Fisenko D.A. — concept and design of the review, writing the text, editing;Kuzenkova L.M. — concept and design of the review, writing the text, editing;Kurenkov A.L. — concept and design of the review, editing;Semikina E.L. — editing;Uvakina E.V. — concept and design of the review, writing the text, editing;Chernikov V.V. — statistical data processing;Kurbatova O.V. — editing;Komyagina T.M. — editing;Konyashin M.V. — editing;Popovich S.G. — editing.All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements

Acknowledgements. The study had no sponsorship.

Conflict of interest

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

Received

Received: March 20, 2025Accepted: April 7, 2025Published: April 30, 2025

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The authors declare that there are no conflicts of interest present.