Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC176810.15690/vramn1768MOLECULAR MEDICINE AND GENETICS: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ГЕНЕТИКИ И МОЛЕКУЛЯРНОЙ МЕДИЦИНЫReview ArticleCurrent Trends in the Diagnosis, Screening and Treatment of Spinal Muscular AtrophyСовременные тенденции в диагностике, скрининге и лечении спинальной мышечной атрофииhttps://orcid.org/0000-0002-7091-11718666-6406MaretinaMarianna A.МаретинаМарианна Александровна
Russian Federation

junior research associate

м.н.с.

marianna0204@gmail.comhttps://orcid.org/0000-0002-2487-24232849-2020KiselevAnton V.КиселевАнтон Вячеславович
Russian Federation

PhD in Biology

к.б.н.

ankiselev@yahoo.co.ukhttps://www.researchgate.net/profile/Anton-Kiselevhttps://orcid.org/0000-0001-5157-5160IlinaArina V.ИльинаАрина Вячеславовна
Russian Federation

лаборант-исследователь

Arina-Ilina-23@yandex.ruhttps://orcid.org/0000-0002-6345-78126055-7399EgorovaAnna A.ЕгороваАнна Алексеевна
Russian Federation

PhD in Biology

к.б.н.

egorova_anna@yahoo.comhttps://orcid.org/0000-0002-7465-45041406-0090GlotovAndrey S.ГлотовАндрей Сергеевич
Russian Federation

PhD in Biology

д.б.н.

anglotov@mail.ruhttps://orcid.org/0000-0002-6542-59534732-8089BespalovaOlesya N.БеспаловаОлеся Николаевна
Russian Federation

MD, PhD

д.м.н.

shiggerra@mail.ruhttps://orcid.org/0000-0002-6518-12079196-7297BaranovVladislav S.БарановВладислав Сергеевич
Russian Federation

MD, PhD, Corresponding Member of the RAS

д.м.н., член-корреспондент РАН

baranov@vb2475.spb.eduhttps://orcid.org/0000-0002-7351-69006572-6450KoganIgor Yu.КоганИгорь Юрьевич
Russian Federation

MD, PhD, Corresponding Member of the RAS

д.м.н., член-корреспондент РАН

ikogan@mail.ruThe Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. OttНИИ акушерства, гинекологии и репродуктологии имени Д.О. Отта2605202277287962510202113042022Copyright ©; 2022, "Paediatrician" Publishers LLCCopyright ©; 2022, Издательство "Педиатръ"2022"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1768

Spinal muscular atrophy is one of the most severe hereditary neuromuscular diseases and one of the main causes of infant mortality caused by hereditary diseases. Being a monogenic disease, SMA is characterized by a wide range of phenotypes, which are based on the influence of genetic modifiers of the disease. These modifiers determine the development of a more severe or milder form of the disease and can act as potential targets of disease therapy. To date, there are three certified drugs for the treatment of SMA, the action of two of them is directed at the transcript of the main modifier of the disease — the SMN2 gene. With the advent of effective therapy, the issue of screening newborns for the purpose of early detection of patients and the beginning of treatment of SMA at the presymptomatic phase to achieve maximum effectiveness of drugs becomes relevant. In addition to neonatal screening, population screening plays an important role, which may result in a decrease in the frequency of births of children with SMA.

Спинальная мышечная атрофия (СМА) является одним из наиболее тяжелых наследственных нервно-мышечных заболеваний и одной из основных причин младенческой смертности, вызванной наследственными заболеваниями. Являясь моногенным заболеванием, СМА характеризуется широким спектром фенотипов, в основе которых лежит влияние генетических модификаторов заболевания. Данные модификаторы определяют развитие более тяжелой или более легкой формы заболевания и могут выступать в качестве потенциальных мишеней его терапии. На сегодняшний день существуют три сертифицированных препарата для терапии СМА, действие двух из них направлено на транскрипт основного модификатора заболевания — гена SMN2. С появлением эффективной терапии актуальным становится вопрос скрининга новорожденных с целью раннего выявления пациентов и начала лечения СМА на пресимптоматической фазе для достижения максимальной эффективности препаратов. Помимо неонатального, важную роль играет популяционный скрининг, результатом которого может быть снижение частоты рождения детей, больных СМА.

spinal muscular atrophydiagnosis of diseasesscreening of diseasestherapy of genetic diseasesneurodegenerative diseasesспинальная мышечная атрофиядиагностика заболеванийскрининг заболеванийтерапия генетических заболеванийнейродегенеративные заболеванияНаучно-исследовательская работаResearch work1021062812133-0-3.2.2Dreesen J, Bras M, de Die-Smulders C, et al. Preimplantation genetic diagnosis of spinal muscular atrophy. Mol Hum Reprod. 1998;4(9):881–885. doi: https://doi.org/10.1093/molehr/4.9.881Wirth B, Karakaya M, Kye MJ, et al. Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next. Annu Rev Genomics Hum Genet. 2020;21:231–261. doi: https://doi.org/10.1146/annurev-genom-102319-103602Lefebvre A, Mauffret O, Hartmann B, et al. Structural behavior of the CpG step in two related oligonucleotides reflects its malleability in solution. Biochemistry. 1995;34(37):12019–12028. doi: https://doi.org/10.1021/bi00037a045Wu X, Wang SH, Sun J, et al. A-44G transition in SMN2 intron 6 protects patients with spinal muscular atrophy. Hum Mol Genet. 2017;26(14):2768–2780. doi: https://doi.org/10.1093/hmg/ddx166Cartegni L, Krainer AR. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat Genet. 2002;30(4):377–384. doi: https://doi.org/10.1038/ng854Cartegni L, Hastings ML, Calarco JA, et al. Determinants of Exon 7 Splicing in the Spinal Muscular Atrophy Genes SMN1 and SMN2. Am J Hum Genet. 2006;78(1):63–77. doi: https://doi.org/10.1086/498853Shababi M, Glascock J, Lorson CL. Combination of SMN Trans-Splicing and a Neurotrophic Factor Increases the Life Span and Body Mass in a Severe Model of Spinal Muscular Atrophy. Hum Gene Ther. 2011;4(22):135–144. doi: https://doi.org/10.1089/hum.2010.114Zarkov M, Stojadinović A, Sekulić S, et al. Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene. Vojnosanit Pregl. 2015;72(10):859–863. doi: https://doi.org/10.2298/vsp140328072zMarkowitz JA, Priyamvada S, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediat Neurol. 2012;46(1):1–12. doi: https://doi.org/10.1016/j.pediatrneurol.2011.09.001Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurol Clin. 2015;33(4):831–846. doi: https://doi.org/10.1016/j.ncl.2015.07.004Zerres K, Rudnik-Schöneborn S, Forrest E, et al. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. 1997;146(1):67–72. doi: https://doi.org/10.1016/S0022-510X(96)00284-5Wijngaarde CA, Veldhoen ES, van Eijk RPA, et al. Natural history of lung function in spinal muscular atrophy. Orphanet J Rare Dis. 2020;15(1):88. doi: https://doi.org/10.1186/s13023-020-01367-yCifuentes-Diaz C, Nicole S, Velasco M, et al. Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model. Hum Mol Genet. 2002;11(12):1439–1447. doi: https://doi.org/10.1093/hmg/11.12.1439Jablonka S, Karle K, Sandner B, et al. Distinct and overlapping alterations in motor and sensory neurons in a mouse model of spinal muscular atrophy. Hum Mol Genet. 2006;15(3):511–518. doi: https://doi.org/10.1093/hmg/ddi467Fletcher EV, Mentis GZ. Motor circuit Dysfunction in Spinal Muscular Atrophy. Sumner CJ, Paushkin S, Ko C-P (eds). Academic Press; 2017. P. 153–165.Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19(1):40–50. doi: https://doi.org/10.1016/j.molmed.2012.11.002Yeo CJJ, Darras BT. Overturning the Paradigm of Spinal Muscular Atrophy as Just a Motor Neuron Disease. Pediatr Neurol. 2020;109:12–19. doi: https://doi.org/10.1016/j.pediatrneurol.2020.01.003Maretina MA, Zheleznyakova GY, Lanko KM, et al. Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates. Curr Genomics. 2018;19(5):339–355. doi: htps://doi.org/10.2174/1389202919666180101154916Hosseinibarkooie S, Peters M, Torres-Benito L, et al. The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype. Am J Hum Genet. 2016;99(3):647–665. doi: https://doi.org/10.1016/j.ajhg.2016.07.014Riessland M, Kaczmarek A, Schneider S, et al. Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis. Am J Hum Genet. 2017;100(2):297–315. doi: https://doi.org/10.1016/j.ajhg.2017.01.005Fan G, Beard C, Chen RZ, et al. Hypomethylation Perturbs the Function and Survival of CNS Neurons in Postnatal Animals. J Neurosci. 2001;21(3):788–797. doi: https://doi.org/10.1523/JNEUROSCI.21-03-00788.2001Ai S, Shen L, Guo J, et al. DNA Methylation as a Biomarker for Neuropsychiatric Diseases. Int J Neurosci. 2012;122(4):165–176. doi: https://doi.org/10.3109/00207454.2011.637654Hauke J, Lunke S, Eyüpoglu IY, et al. Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet. 2009;18(2):304–317. doi: https://doi.org/10.1093/hmg/ddn357Zheleznyakova GY, Voisin S, Kiselev AV, et al. Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity. Eur J Hum Genet. 2013;21(9):988–993. doi: https://doi.org/10.1038/ejhg.2012.293Zheleznyakova GY, Nilsson EK, Kiselev AV, et al. Methylation Levels of SLC23A2 and NCOR2 Genes Correlate with Spinal Muscular Atrophy Severity. PLoS One. 2015;10(3):e0121964. doi: https://doi.org/10.1371/journal.pone.0121964Maretina M, Egorova A, Baranov V, et al. DYNC1H1 gene methylation correlates with severity of spinal muscular atrophy. Ann Hum Genet. 2019;83(2):73– 81. doi: https://doi.org/10.1111/ahg.12288Peters M. Combined therapy of SMN-ASO and Plastin 3 overexpression rescues severe SMA in mice [dissertation]. University of Cologne; 2017.Torres-Benito L, Schneider S, Rombo R, et al. Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice. Am J Hum Genet. 2019;105(1):221–230. doi: https://doi.org/10.1016/j.ajhg.2019.05.008Van der Steege G, Grootscholten PM, van der Vlies P, et al. PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet. 1995;345(8955):985–986. doi: https://doi.org/10.1016/S0140-6736(95)90732-7Глотов А.С., Киселев А.В., Иващенко Т.Э., Баранов В.С. Анализ делеционных повреждений в генах SMN1, SMN2 и NAIP у пациентов со спинальной мышечной атрофией северо-западного региона России // Генетика. – 2001. – Т. 37. – № 8. — С. 1156–1159 [Glotov AS, Kiselev AV, Ivaschenko TE, et al. Analysis of deletions in SMN1, SMN2, and NAIP genes in spinal muscular atrophy patients from the northwestern region of Russia. Russian Journal of Genetics. 2001;37(8):968–971. (In Russ.)]. doi: https://doi.org/10.1023/A:1016794120171Anhuf D, Eggermann T, Rudnik-Schöneborn S, et al. Determination of SMN1 and SMN2 copy number using TaqMan™ technology. Hum Mutat. 2003;22(1):74–78. doi: https://doi.org/10.1002/humu.10221mrcholland.com [Internet]. MRC Holland. Availabe from: mrcholland.comWirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat. 2000;15(3):228–237. doi: https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9Маретина M.А., Киселев А.В., Железнякова Г.Ю., и др. Определение количества копий гена SMN2 у больных спинальной мышечной атрофией Северо-Западного региона России // Медицинская генетика. — 2012. — № 4. — С. 25–28. [Maretina MA, Kiselev AV, Zheleznyakova GY, et al. Determination of SMN2 gene copy number in spinal muscular atrophy patients of North-Western region of Russia. Medical Genetics. 2012;(4):25–28. (In Russ.)]Parks M, Court S, Bowns B, et al. Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage. Eur J Hum Genet. 2017;25(4):416–422. doi: https://doi.org/10.1038/ejhg.2016.195Козюлина П.Ю., Вашукова Е.С., Моршнева А.В., и др. Опыт применения NGS секвенирования для проведения НИПТ на базе ФГНУ «НИИ АГиР им. Д.О. Отта» // Медицинская генетика. — 2020. — Т. 9. — № 3. — С. 71–73. [Kozyulina PY, Vashukova ES, Morshneva AV, et al. Application of NiPt by NGS sequencing in D.O. Ott Research Institute for Obstetrics, Gynaecology and Reproductology. Medical Genetics. 2020;9(3):71–73. (In Russ.)]Баранов В.С., Кузнецова Т.В., Кащеева Т.К., и др. Пренатальная диагностика наследственных болезней. Состояние и перспективы. — 3-е изд., перераб. и доп. — СПб.: Эко-Вектор, 2020. [Baranov VS, Kuznecova TV, Kashcheeva TK, i dr. Prenatal’naya diagnostika nasledstvennyh boleznej. Sostoyanie i perspektivy. 3-e izd., pererab. i dop. Saint Petesburg: Eko-Vektor: 2020. (In Russ.)]Коган И.Ю., Яковлев П.П., Гзгзян А.М., и др. Преимплантационное генетичеcкое тестирование моногенных заболеваний. Описание клинического случая // Журнал акушерства и женских болезней. — 2018. — Т. 67. — № 1. — С. 92–95. [Коgan IYu, Iakovlev PP, Gzgzyan АМ, et al. A preimplantation genetic testing of monogenic diseases. Description of clinical case. Journal of Obstetrics and Women’s Diseases. 2017;67(1):92–95. (In Russ).] doi: https://doi.org/10.17816/JOWD67192-95Theodosiou AM, Morrison KE, Nesbit AM, et al. Complex repetitive arrangements of gene sequence in the candidate region of the spinal muscular atrophy gene in 5q13. Am J Hum Genet. 1994;55(6):1209–1217.Francis MJ, Nesbit MA, Theodosiou AM, et al. Mapping of Retrotransposon Sequences in the Unstable Region Surrounding the Spinal Muscular Atrophy Locus in 5q13. Genomics. 1995;27(2):366–369. doi: https://doi.org/10.1006/geno.1995.1059Van der Steege G, Grootscholten PM, Cobben JM, et al. Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5. Am J Hum Genet. 1996;59(4):834–838.Глотов А.С., Киселев А.В., Иващенко Т.Э., Баранов В.С. Анализ конверсий в генах SMN1 и SMN2 при спинальной мышечной атрофии // Медицинская генетика. — 2004. — Т. 3.— № 2. — С. 78–83. [Glotov AS. Kiselev AV. Ivashchenko TE. Baranov VS. Analiz konversiy v genakh SMN1 i SMN2 pri spinalnoy myshechnoy atrofii. Meditsinskayagenetika. 2004;3(2): 78–83. (In Russ).]Баранов В.С., Кащеева Т.К., Кузнецова Т.В. Достижения, сенсации и трудности пренатальной молекулярно-генетической диагностики // Журнал акушерства и женских болезней. — 2016. — Т. 65. — № 2. — С. 70–80. [Baranov VS, Kashcheyeva TK, Kuznetsova TV. Dostizheniya, sensatsii I trudnosti prenatalnoy molekulyarno-geneticheskoy diagnostiki. Zhurnal akusherstva i zhenskikh bolezney. 2016;65(2):70–80. (In Russ.)]Hendrickson BC, Donohoe C, Akmaev VR, et al. Differences in SMN1 allele frequencies among ethnic groups within North America. Journal of Medical Genetics. 2009;46(9):641–644. doi: https://doi.org/10.1136/jmg.2009.066969Prior TW, Nagan N. Spinal muscular atrophy: Overview of molecular diagnostic approaches. Curr Protoc Hum Genet. 2016;88:9.27.1–9.27.13. doi: https://doi.org/10.1002/0471142905.hg0927s88Melki J, Lefebvre S, Burglen L, et al. De Novo and Inherited Deletions of the 5q13 Region in Spinal Muscular Atrophies. Science. 1994;264(5164):1474–1477. doi: https://doi.org/10.1126/science.7910982Matthijs G, Schollen E, Legius E, et al. Unusual molecular findings in autosomal recessive spinal muscular atrophy. J Med Genet. 1996;33(6):469–474. doi: https://doi.org/10.1136/jmg.33.6.469Brichta L. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet. 2003;12(19):2481–2489. doi: https://doi.org/10.1093/hmg/ddg256Sumner CJ, Huynh TN, Markowitz JA, et al. Valproic Acid Increases SMN Levels in Spinal Muscular Atrophy Patient Cells. Ann Neurol. 2003;54(5):647–654. doi: https://doi.org/10.1002/ana.10743Баранов В.С., Вахарловский В.Г., Команцев В.Н. Первый опыт лечения больных спинальной мышечной атрофией препаратом вальпроевой кислоты // Медицинская генетика. — 2005. [Baranov VS, Vakharlovskiy VG, Komantsev VN. Pervyy opyt lecheniya bolnykh spinalnoy myshechnoy atrofiyey preparatom valproyevoy kisloty. Meditsinskaya genetika. 2005. (In Russ.)]Вахарловский В.Г., Команцев В.Н., Любименко В.А., и др. Современные клинико-терапевтические вопросы проксимальной спинальной мышечной атрофии // Нейрохирургия и неврология. — 2008. — С. 38–48. [Vakharlovskiy VG, Komantsev VN, Lyubimenko VA. i dr. Sovremennyye kliniko-terapevticheskiye voprosy proksimalnoy spinalnoy myshechnoy atrofii. Neyrokhirurgiya i nevrologiya. 2008:38–48. (In Russ.)]Swoboda KJ, Scott CB, Crawford TO, et al. SMA CARNI-VAL Trial Part I: Double-Blind, Randomized, Placebo-Controlled Trial of L-Carnitine and Valproic Acid in Spinal Muscular Atrophy. PLoS One. 2010;5(8):e12140. doi: https://doi.org/10.1371/journal.pone.0012140Kissel JT, Scott CB, Reyna SP, et al. SMA CARNI-VAL TRIAL PART II: A Prospective, Single-Armed Trial of L-Carnitine and Valproic Acid in Ambulatory Children with Spinal Muscular Atrophy. PLoS One. 2011;6(7):e21296. doi: https://doi.org/10.1371/journal.pone.0021296Kissel JT, Elsheikh B, King WM, et al. SMA valiant trial: A prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy. Muscle Nerve. 2014;49(2):187–192. doi: https://doi.org/10.1002/mus.23904Krosschell KJ, Kissel JT, Townsend EL, et al. Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I. Muscle Nerve. 2018;57(2):193–199. doi: https://doi.org/10.1002/mus.25776Finkel RS, Mercuri E, Darras BT. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1723. doi: https://doi.org/10.1056/NEJMoa1702752Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018;378(7):625–635. doi: https://doi.org/10.1056/NEJMoa1710504De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety resultsfrom the Phase 2 nurture study. Neuromuscul Disord. 2019;29(11):842–856. doi: https://doi.org/10.1016/j.nmd.2019.09.007Wirth B. Spinal Muscular Atrophy: In the Challenge Lies a Solution. Trends Neurosci. 2021;44(4):306–322. doi: https://doi.org/10.1016/j.tins.2020.11.009Mendell JR, Samiah A-Z, Richard S, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1713. doi: https://doi.org/10.1056/NEJMoa1706198Day JW, Finkel RS, Mercuri E, et al. Adeno-associated virus serotype 9 antibodies in patients screened for treatment with onasemnogene abeparvovec, Mol Ther Methods Clin Dev. 2021;21:76–82. doi: https://doi.org/10.1016/j.omtm.2021.02.014Kichula EA, Proud CM, Farrar MA, et al. Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy. Muscle Nerve. 2021;64(4):413–427. doi: https://doi.org/10.1002/mus.27363Ratni H, Ebeling M, Baird J, et al. Discovery of Risdiplam a Selective Survival of Motor Neuron-2 SMN2 Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2018;61(15):6501–6517. doi: https://doi.org/10.1021/acs.jmedchem.8b00741Seabrook T, Baranello G, Servais L, et al. 1-year results on motor function in infants with Type 1 spinal muscular atrophy (SMA) receiving risdiplam (RG7916). Canadian Journal of Neurological Sciences. Journal Canadien des Sciences Neurologiques. 2019;46(S1):S31–S31. doi: https://doi.org/10.1017/cjn.2019.164roche.com [Internet]. Roche — Media releases & Ad hoc announcements. Available from: https://www.roche.com/media/releasesChen T-H. New and Developing Therapies in Spinal Muscular Atrophy: From Genotype to Phenotype to Treatment and Where Do We Stand? Int J Mol Sci. 2020;21(9):3297. doi: https://doi.org/10.3390/ijms21093297Valetdinova KR, Maretina MA, Kuranova ML, et al. Generation of two spinal muscular atrophy (SMA) type I patient-derived induced pluripotent stem cell (iPSC) lines and two SMA type II patient-derived iPSC lines. Stem Cell Res. 2019;34:101376. doi: https://doi.org/10.1016/j.scr.2018.101376Ovechkina VS, Maretina MA, Egorova AA, et al. Generation of a spinal muscular atrophy type III patient-specific induced pluripotent stem cell line ICGi003-A. Stem Cell Res. 2020;48:101938. doi: https://doi.org/10.1016/j.scr.2020.101938Григорьева Е.В., Валетдинова К.Р., Устьянцева Е.И., и др. Дифференцировка в нейральном направлении пациент-специфичных индуцированных плюрипотентных стволовых клеток от больных с наследственной формой спинальной мышечной атрофии // Гены & клетки. — 2016. — Т. 11. — № 2. — С. 70–79. [Grigorieva EV, Valetdinova KR, Ustyantseva EI, et al. Differentiation in the neural direction of patient-specific induced pluripotent stem cells from patients with a hereditary form of spinal muscular atrophy. Genes & Cells. 2016;11(2):70–79. (In Russ.)]Corti S, Nizzardo M, Nardini M, et al. Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy. J Clin Invest. 2008;118(10):3316–3330. doi: https://doi.org/10.1172/JCI35432Egorova AA, Shtykalova SV, Maretina MA, et al. Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma. Mol Biol (Mosk). 2020;54(3):497–511. doi: https://doi.org/10.1134/S0026893320030064Крылова Н.В., Маретина М.А., Ильина А.В., и др. Анализ уровня транскриптов и белка SMN в фибробластах, полученных от пациентов со спинальной мышечной атрофией, после доставки терапевтических антисмысловых олигонуклеотидов // Всероссийский форум «Педиатрия Санкт-Петербурга: опыт, инновации, достижения», 27–28 сентября 2019 г., Санкт-Петербург. [Krylova NV, Maretina MA, Ilina AV, i dr. Analiz urovnya transkriptov I belka SMN v fibroblastakh, poluchennykh ot patsiyentov so spinalnoy myshechnoy atrofiyey, posle dostavki terapevticheskikh antismyslovykh oligonukleotidov. Vserossiyskiy forum “Pediatriya Sankt-Peterburga: opyt. innovatsii. dostizheniya”, 2019 Sent. 27–28, Sankt-Peterburg. (In Russ.)]Ильина А.В., Маретина М.А., Крылова Н.В., и др. Воздействие на сайленсеры сплайсинга гена SMN2 антисмысловыми LNA-олигонуклеотидами для увеличения уровня полноразмерных транскриптов SMN в фибробластах пациентов со СМА // Материалы 22-й Межвузовской студенческой научной конференции «Студент–исследователь–учитель», 1–30 апреля 2020 г. [Ilina AV, Maretina MA, Krylova NV, et al. Impact of antisense LNA-oligonucleotides on splicing silencers of SMN2 gene for increasing of SMN full-length transcripts level in fibroblasts of SMA patients. Materialy 22 Mezhvuzovskoy studencheskoy nauchnoy konferentsii “Student–issledovatel–uchitel”, 2020 March 1–30, Saint Peterburg. (In Russ.)]Farrelly-Rosch A, Lau CL, Patil N, et al. Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts. Neurochem Int. 2017;108:213–221. doi: https://doi.org/10.1016/j.neuint.2017.02.016Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: World Health Orgaization; 1968.Govoni A, Gagliardi D, Comi GP, et al. Time Is Motor Neuron: Therapeutic Window and Its Correlation with Pathogenetic Mechanisms in Spinal Muscular Atrophy. Mol Neurobiol. 2018;55(8):6307–6318. doi: https://doi.org/10.1007/s12035-017-0831-9Swoboda, KJ, Prior TW, Scott CB, et al. Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function. Ann Neurol. 2005;57(5):704–712. doi: https://doi.org/10.1002/ana.20473Butterfield RJ. Spinal Muscular Atrophy Treatments, Newborn Screening, and the Creation of a Neurogenetics Urgency. Semin Pediatr Neurol. 2021;38:100899. doi: https://doi.org/10.1016/j.spen.2021.100899Lin C-W, Kalb SJ, Yeh W-S. Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. Pediatr Neurol. 2015;53(4):293–300. doi: https://doi.org/10.1016/j.pediatrneurol.2015.06.002Chien Y-H, Chiang S-C, Weng W-C, et al. Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening. J Pediatr. 2017;190:124–129.e1. doi: https://doi.org/10.1016/j.jpeds.2017.06.042Kraszewski J, Kay D, Stevens C, et al. Pilot study of population-based newborn screening for spinal muscular atrophy in New York state. Genet Med. 2018;20(6):608–613. doi: https://doi.org/10.1038/gim.2017.152Hale K, Ojodu J, Singh S. Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021. Int J Neonatal Screen. 2021;7(3):33. doi: https://doi.org/10.3390/ijns7030033curesma.org. [Internet]. Cure SMA. Available from: www.curesma.orgVill K, Schwartz O, Blaschek A, et al. Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years. Orphanet J Rare Dis. 2021;16(1):153. doi: https://doi.org/10.1186/s13023-021-01783-8Boemer F, Caberg J-H, Dideberg V, et al. Newborn screening for SMA in Southern Belgium. Neuromuscul Disord. 2019;29(5):343–349. doi: https://doi.org/10.1016/j.nmd.2019.02.003Kariyawasam DST, Russell JS, Wiley V, et al. The implementation of newborn screening for spinal muscular atrophy: the Australian experience. Genet Med. 2020;22(3):557–565. doi: https://doi.org/10.1038/s41436-019-0673-0Поляков А.В. Уроки программы по неонатальному скринингу в г. Москве // Материалы VI всероссийской конференции «Орфаника-2021», 9 сентября 2021 г. [Polyakov AV. Uroki programmy po neonatalnomu skriningu v g. Moskve. Materialy VI vserossiyskoy konferentsii “Orfanika-2021”, 2021 Sent. 9, Moskva (In Russ.)]. Available from: https:// https://ormiz.ru/orfanica6/#programme#!/tab/329546403-2Dangouloff T, Vrščaj E, Servais L, et al. Newborn screening programs for spinal muscular atrophy worldwide: Where we stand and where to go. Neuromuscul Disord. 2021;31(6):574–582. doi: https://doi.org/10.1016/j.nmd.2021.03.007Кобякова О.С., Стародубов В.И., Зеленова О.В., и др. Поперечное исследование «Федеральный регистр пациентов с генетически подтвержденным диагнозом спинально-мышечная атрофия ФРПСМА»: обоснование и дизайн исследования. Первые результаты // Современные проблемы здравоохранения и медицинской статистики. — 2021. — № 2. — С. 279–300. [Kobyakova OS, Starodubov VI, Zelenova OV, et al. Prospective study “Federal register of patients with a genetically confirmed diagnosis of spinal muscular atrophy FRPSMA”: the basis and design of the study. first results. Current Problems of Health Care and Medical Statistics. 2021;2:279–300. (In Russ.)]