neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2023-4-3-130-136epnbqaneurojour-104Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSНейрофиламенты как биомаркер спинальной мышечной атрофииNeurofilaments as a biomarker of spinal muscular atrophy: reviewhttps://orcid.org/0000-0002-7893-1863ФисенкоДарья АндреевнаFisenkoDaria A.

Аспирант Центра детской психоневрологии ФГАУ «НМИЦ здоровья детей», 119296, Москва.

e-mail: fisenko.daria@mail.ru

 

Postgraduate student 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 М.KuzenkovaLyudmila M.noemail@neicon.ruhttps://orcid.org/0000-0002-7269-9100КуренковАлексей Л.KurenkovAlexey L.noemail@neicon.ruhttps://orcid.org/0000-0002-8381-8793УвакинаЕвгения В.UvakinaEugeniya V.noemail@neicon.ruhttps://orcid.org/0000-0002-9697-500XПоповичСофия Г.PopovichSophia G.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center for Children’s Health, of the Ministry of Health of the Russian FederationRussian FederationФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России; Клинический институт детского здоровья имени Н.Ф. Филатова ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияNational Medical Research Center for Children’s Health, of the Ministry of Health of the Russian Federation; N.F. Filatov Clinical Institute of Children’s Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)Russian Federation20231910202343130136Copyright © Фисенко Д.А., Кузенкова Л.М., Куренков А.Л., Увакина Е.В., Попович С.Г., 20232023Фисенко Д.А., Кузенкова Л.М., Куренков А.Л., Увакина Е.В., Попович С.Г.Fisenko D.A., Kuzenkova L.M., Kurenkov A.L., Uvakina E.V., Popovich S.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/104

Спинальная мышечная атрофия (СМА) — аутосомно-рецессивное инвалидизирующее нервно-мышечное заболевание, которое характеризуется гибелью мотонейронов в спинном мозге, что приводит к развитию мышечной слабости и впоследствии к развитию вялого тетрапареза, нарушениям глотания и дыхания. Различают 4 типа СМА в зависимости от возраста манифестации, наиболее тяжёлым считается I тип заболевания.

Современная диагностика СМА включает молекулярно-генетическое исследование с поиском мутаций в гене SMN1 и определением числа копий гена SMN2. Инструментальные и биохимические методы оценки эффективности терапии СМА находятся в стадии изучения. Белки нейрофиламентов были исследованы в качестве потенциальных биомаркеров нескольких заболеваний, характеризую­щихся повреждением и дегенерацией аксонов. В клинических исследованиях есть единичные данные об использовании нейрофиламентов крови как маркеров СМА. В данном обзоре рассматриваются данные зарубежных авторов и клинические исследования нейрофиламентов в качестве перспективных биомаркеров СМА — как тяжёлых, так и лёгких цепей.

Участие авторов

Участие авторов:Фисенко Д.А. — концепция и дизайн статьи, написание текста, редактирование;Кузенкова Л.М. — концепция и дизайн статьи, редактирование;Куренков А.Л. — концепция и дизайн статьи, редактирование;Увакина Е.В. — концепция и дизайн статьи, редактирование;Попович С.Г. — концепция и дизайн статьи, редактирование.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Конфликт интересов

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

Поступила 10

Поступила 10.06.2023Принята к печати 15.08.2023Опубликована 13.10.2023

Spinal muscular atrophy (SMA) is an autosomal recessive, disabling neuromuscular disease characterized by the death of motor neurons in the spinal cord, giving rise in the development both of muscle weakness and, subsequently, flaccid tetraparesis, swallowing and breathing disorders. There are 4 types of SMA, depending on the age of manifestation, the most severe is type I (not counting type 0 — prenatal type).

Modern diagnosis of SMA includes a molecular genetic study looking for mutations in the SMN1 gene and determining the copy number of the SMN2 gene. Instrumental and biochemical methods for evaluating the effectiveness of therapy for spinal muscular atrophy are currently under study. Neurofilament proteins have been investigated as potential biomarkers for several diseases characterized by axonal damage and degeneration. In clinical studies, there are isolated data on the use of blood neurofilaments as markers of SMA. This review considers the literature data of foreign authors and clinical studies of neurofilaments as perspective biomarkers of SMA, both heavy and light chains.

Contribution

Contribution:Fisenko D.A. — concept and design of the review, writing the text, editing;Kuzenkova L.M. — concept and design of the review, editing;Kurenkov A.L. — concept and design of the review, editing;Uvakina E.V. — concept and design of the review, editing;Popovich S.G. — concept and design of the review, 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: June10, 2023Accepted: August 30, 2023Published: October 13, 2023

спинальная мышечная атрофиябиомаркернейрофиламентынусинерсенонасемноген абепарвовектяжёлые цепилёгкие цепиspinal muscular atrophySMAbiomarkersneurofilamentsnusinersenonasemnogene abeparvovecheavy chainslight chainsNFReferencesMendell J.R., Al-Zaidy S.A., Lehman K.J., McColly M., Lowes L.P., Alfano L.N., et al. Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy. JAMA Neurol. 2021; 78(7): 834–41. https://doi.org/10.1001/jamaneurol.2021.1272Mendell J.R., Al-Zaidy S.A., Lehman K.J., McColly M., Lowes L.P., Alfano L.N., et al. Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy. JAMA Neurol. 2021; 78(7): 834–41. https://doi.org/10.1001/jamaneurol.2021.1272Calucho M., Bernal S., Alías L., March F., Venceslá A., Rodríguez-Álvarez F.J., et al. Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2,834 reported cases. Neuromuscul. Disord. 2018; 28(3): 208–15. https://doi.org/10.1016/j.nmd.2018.01.003Calucho M., Bernal S., Alías L., March F., Venceslá A., Rodríguez-Álvarez F.J., et al. Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2,834 reported cases. Neuromuscul. Disord. 2018; 28(3): 208–15. https://doi.org/10.1016/j.nmd.2018.01.003Friese J., Geitmann S., Holzwarth D., Müller N., Sassen R., Baur U., et al. Safety monitoring of gene therapy for spinal muscular atrophy with onasemnogene abeparvovec – a single centre experience. J. Neuromuscul. Dis. 2021; 8(2): 209–16. https://doi.org/10.3233/jnd-200593Friese J., Geitmann S., Holzwarth D., Müller N., Sassen R., Baur U., et al. Safety monitoring of gene therapy for spinal muscular atrophy with onasemnogene abeparvovec – a single centre experience. J. Neuromuscul. Dis. 2021; 8(2): 209–16. https://doi.org/10.3233/jnd-200593Wirth B., Herz M., Wetter A., Moskau S., Hahnen E., Rudnik-Schöneborn S., et al. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am. J. Hum. Genet. 1999; 64(5): 1340–56. https://doi.org/10.1086/302369Wirth B., Herz M., Wetter A., Moskau S., Hahnen E., Rudnik-Schöneborn S., et al. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am. J. Hum. Genet. 1999; 64(5): 1340–56. https://doi.org/10.1086/302369Ferreira-Atuesta C., Reyes S., Giovanonni G., Gnanapavan S. The evolution of neurofilament light chain in multiple sclerosis. Front. Neurosci. 2021; 15: 642384. https://doi.org/10.3389/fnins.2021.642384Ferreira-Atuesta C., Reyes S., Giovanonni G., Gnanapavan S. The evolution of neurofilament light chain in multiple sclerosis. Front. Neurosci. 2021; 15: 642384. https://doi.org/10.3389/fnins.2021.642384Khalil M., Teunissen C.E., Otto M., Piehl F., Sormani M.P., Gattringer T., et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 2018; 14(10): 577–89. https://doi.org/10.1038/s41582-018-0058-zKhalil M., Teunissen C.E., Otto M., Piehl F., Sormani M.P., Gattringer T., et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 2018; 14(10): 577–89. https://doi.org/10.1038/s41582-018-0058-zYuan A., Nixon R.A. Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front. Neurosci. 2021; 15: 689938. https://doi.org/10.3389/fnins.2021.689938Yuan A., Nixon R.A. Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front. Neurosci. 2021; 15: 689938. https://doi.org/10.3389/fnins.2021.689938Hviid C.V.B., Knudsen C.S., Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand. J. Clin. Lab. Invest. 2020; 80(4): 291–5. https://doi.org/10.1080/00365513.2020.1730434Hviid C.V.B., Knudsen C.S., Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand. J. Clin. Lab. Invest. 2020; 80(4): 291–5. https://doi.org/10.1080/00365513.2020.1730434Воробьева А.А., Иванова М.В., Фоминых В.В., Захарова М.Н., Зигангирова Н.А., Гуляева Н.В. Биомаркеры рассеянного склероза (обзор и собственные данные). Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2013; 113(10‑2): 23–31. https://elibrary.ru/rtekrhVorob’eva A.A., Ivanova M.V., Fominykh V.V., Zakharova M.N., Zigangirova N.A., Gulyaeva N.V. Biomarkers in multiple sclerosis (a review and experimental data). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. Spetsvypuski. 2013; 113(10‑2): 23–31. https://elibrary.ru/rtekrh (in Russian)Gafson A.R., Barthélemy N.R., Bomont P., Carare R.O., Durham H.D., Julien J.P., et al. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020; 143(7): 1975–98. https://doi.org/10.1093/brain/awaa098Gafson A.R., Barthélemy N.R., Bomont P., Carare R.O., Durham H.D., Julien J.P., et al. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020; 143(7): 1975–98. https://doi.org/10.1093/brain/awaa098Darras B.T., Crawford T.O., Finkel R.S., Mercuri E., De Vivo D.C., Oskoui M., et al. Neurofilament as a potential biomarker for spinal muscular atrophy. Ann. Clin. Transl. Neurol. 2019; 6(5): 932–44. https://doi.org/10.1002/acn3.779Darras B.T., Crawford T.O., Finkel R.S., Mercuri E., De Vivo D.C., Oskoui M., et al. Neurofilament as a potential biomarker for spinal muscular atrophy. Ann. Clin. Transl. Neurol. 2019; 6(5): 932–44. https://doi.org/10.1002/acn3.779Matsushige T., Inoue H., Fukunaga S., Hasegawa S., Okuda M., Ichiyama T. Serum neurofilament concentrations in children with prolonged febrile seizures. J. Neurol. Sci. 2012; 321(1-2): 39–42. https://doi.org/10.1016/j.jns.2012.07.043Matsushige T., Inoue H., Fukunaga S., Hasegawa S., Okuda M., Ichiyama T. Serum neurofilament concentrations in children with prolonged febrile seizures. J. Neurol. Sci. 2012; 321(1-2): 39–42. https://doi.org/10.1016/j.jns.2012.07.043Douglas-Escobar M., Yang C., Bennett J., Shuster J., Theriaque D., Leibovici A., et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr. Res. 2010; 68(6): 531–6. https://doi.org/10.1203/pdr.0b013e3181f85a03Douglas-Escobar M., Yang C., Bennett J., Shuster J., Theriaque D., Leibovici A., et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr. Res. 2010; 68(6): 531–6. https://doi.org/10.1203/pdr.0b013e3181f85a03Toorell H., Zetterberg H., Blennow K., Savman K., Hagberg H. Increase of neuronal injury markers Tau and neurofilament light proteins in umbilical blood after intrapartum asphyxia. J. Matern. Fetal Neonatal Med. 2018; 31(18): 2468–72. https://doi.org/10.1080/14767058.2017.1344964Toorell H., Zetterberg H., Blennow K., Savman K., Hagberg H. Increase of neuronal injury markers Tau and neurofilament light proteins in umbilical blood after intrapartum asphyxia. J. Matern. Fetal Neonatal Med. 2018; 31(18): 2468–72. https://doi.org/10.1080/14767058.2017.1344964Shah D.K., Ponnusamy V., Evanson J., Kapellou O., Ekitzidou G., Gupta N., et al. Raised plasma neurofilament light protein levels are associated with abnormal MRI outcomes in newborns undergoing therapeutic hypothermia. Front. Neurol. 2018; 9: 86. https://doi.org/10.3389/fneur.2018.00086Shah D.K., Ponnusamy V., Evanson J., Kapellou O., Ekitzidou G., Gupta N., et al. Raised plasma neurofilament light protein levels are associated with abnormal MRI outcomes in newborns undergoing therapeutic hypothermia. Front. Neurol. 2018; 9: 86. https://doi.org/10.3389/fneur.2018.00086Sandelius A., Zetterberg H., Blennow K., Adiutori R., Malaspina A., Laura M., et al. Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology. 2018; 90(6): e518–24. https://doi.org/10.1212/wnl.0000000000004932Sandelius A., Zetterberg H., Blennow K., Adiutori R., Malaspina A., Laura M., et al. Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology. 2018; 90(6): e518–24. https://doi.org/10.1212/wnl.0000000000004932Schulpis K.H., Margeli A., Akalestos A., Vlachos G.D., Partsinevelos G.A., Papastamataki M., et al. Effects of mode of delivery on maternal-neonatal plasma antioxidant status and on protein S100B serum concentrations. Scand. J. Clin. Lab. Invest. 2006; 66(8): 733–42. https://doi.org/10.1080/00365510600977737Schulpis K.H., Margeli A., Akalestos A., Vlachos G.D., Partsinevelos G.A., Papastamataki M., et al. Effects of mode of delivery on maternal-neonatal plasma antioxidant status and on protein S100B serum concentrations. Scand. J. Clin. Lab. Invest. 2006; 66(8): 733–42. https://doi.org/10.1080/00365510600977737Depoorter A., Neumann R.P., Barro C., Fisch U., Weber P., Kuhle J., et al. Neurofilament light chain: blood biomarker of neonatal neuronal injury. Front. Neurol. 2018; 9: 984. https://doi.org/10.3389/fneur.2018.00984Depoorter A., Neumann R.P., Barro C., Fisch U., Weber P., Kuhle J., et al. Neurofilament light chain: blood biomarker of neonatal neuronal injury. Front. Neurol. 2018; 9: 984. https://doi.org/10.3389/fneur.2018.00984Evers K.S., Hügli M., Fouzas S., Kasser S., Pohl C., Stoecklin B., et al. Serum neurofilament levels in children with febrile seizures and in controls. Front. Neurosci. 2020; 14: 579958. https://doi.org/10.3389/fnins.2020.579958Evers K.S., Hügli M., Fouzas S., Kasser S., Pohl C., Stoecklin B., et al. Serum neurofilament levels in children with febrile seizures and in controls. Front. Neurosci. 2020; 14: 579958. https://doi.org/10.3389/fnins.2020.579958Khalil M., Pirpamer L., Hofer E., Voortman M.M., Barro C., Leppert D., et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat. Commun. 2020; 11(1): 812. https://doi.org/10.1038/s41467-020-14612-6Khalil M., Pirpamer L., Hofer E., Voortman M.M., Barro C., Leppert D., et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat. Commun. 2020; 11(1): 812. https://doi.org/10.1038/s41467-020-14612-6Reinert M.C., Benkert P., Wuerfel J., Michalak Z., Ruberte E., Barro C., et al. Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2020; 7(4): e749. https://doi.org/10.1212/nxi.0000000000000749Reinert M.C., Benkert P., Wuerfel J., Michalak Z., Ruberte E., Barro C., et al. Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2020; 7(4): e749. https://doi.org/10.1212/nxi.0000000000000749Alves C.R.R., Petrillo M., Spellman R., Garner R., Zhang R., Kiefer M., et al. Implications of circulating neurofilaments for spinal muscular atrophy treatment early in life: A case series. Mol. Ther. Methods Clin. Dev. 2021; 23: 524–38. https://doi.org/10.1016/j.omtm.2021.10.011Alves C.R.R., Petrillo M., Spellman R., Garner R., Zhang R., Kiefer M., et al. Implications of circulating neurofilaments for spinal muscular atrophy treatment early in life: A case series. Mol. Ther. Methods Clin. Dev. 2021; 23: 524–38. https://doi.org/10.1016/j.omtm.2021.10.011Spicer C., Lu C.H., Catapano F., Scoto M., Zaharieva I., Malaspina A., et al. The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy. Ann. Clin. Transl. Neurol. 2021; 8(4): 866–76. https://doi.org/10.1002/acn3.51336Spicer C., Lu C.H., Catapano F., Scoto M., Zaharieva I., Malaspina A., et al. The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy. Ann. Clin. Transl. Neurol. 2021; 8(4): 866–76. https://doi.org/10.1002/acn3.51336Finkel R.S., Ryan M.M., Pascual Pascual S.I., Day J.W., Mercuri E., De Vivo D.C., et al. Scientific rationale for a higher dose of nusinersen. Ann. Clin. Transl. Neurol. 2022; 9(6): 819–29. https://doi.org/10.1002/acn3.51562Finkel R.S., Ryan M.M., Pascual Pascual S.I., Day J.W., Mercuri E., De Vivo D.C., et al. Scientific rationale for a higher dose of nusinersen. Ann. Clin. Transl. Neurol. 2022; 9(6): 819–29. https://doi.org/10.1002/acn3.51562De Vivo D.C., Bertini E., Swoboda K.J., Hwu W.L., Crawford T.O., Finkel R.S., et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul. Disord. 2019; 29(11): 842–56. https://doi.org/10.1016/j.nmd.2019.09.007De Vivo D.C., Bertini E., Swoboda K.J., Hwu W.L., Crawford T.O., Finkel R.S., et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul. Disord. 2019; 29(11): 842–56. https://doi.org/10.1016/j.nmd.2019.09.007

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