{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:25:26Z","timestamp":1778498726215,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a genetic neuromuscular disease resulting in global muscular weakness and, frequently, in respiratory failure and premature death. Gene-based therapies like Nusinersen are now available for patients with SMA. The aim of this review was to assess in \u201creal world\u201d studies, whether novel treatments would have a positive impact on the mechanical ventilatory support requirements of SMA patients, already initiated on ventilatory support prior to treatment administration. A literature search was performed in Pubmed using multiple combinations of MESH terms and the snowball procedure. A total of 14 publications were discussed in this review. Considering all patients included in the published studies who were on ventilatory support and were treated with Nusinersen, 13\/172 (7.5%) had reduced needs for ventilatory support, 1\/172 (0.6%) did not need ventilation post-treatment, and 122\/172 (70.9%) were maintained on the same ventilator settings. Moreover, 2\/41 (4.9%) children who were offered gene therapy had no need for further ventilatory support and 12\/41 (29.2%) had reduced requirements. In conclusion, available evidence suggests that among children with SMA, who are on mechanical respiratory support either noninvasively or via tracheostomy at the time of gene-based treatment, only a few will be weaned off the ventilator or have reduced ventilator needs per 24 h. Children will usually require the same level of support as before treatment.<\/jats:p>","DOI":"10.3390\/children9081207","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:15:05Z","timestamp":1660252505000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-167X","authenticated-orcid":false,"given":"Panagiota","family":"Panagiotou","sequence":"first","affiliation":[{"name":"Department on Pediatric Respiratory Medicine, Evelina London Children\u2019s Hospital, London SE1 7EH, UK"},{"name":"Division of Pediatric Pulmonology and Sleep Disorders Laboratory, First Department of Pediatrics, Agia Sofia Children\u2019s Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-6470","authenticated-orcid":false,"given":"Christina","family":"Kanaka-Gantenbein","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology and Sleep Disorders Laboratory, First Department of Pediatrics, Agia Sofia Children\u2019s Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3592-0037","authenticated-orcid":false,"given":"Athanasios G.","family":"Kaditis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology and Sleep Disorders Laboratory, First Department of Pediatrics, Agia Sofia Children\u2019s Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1136\/thoraxjnl-2012-201964","article-title":"British Thoracic Society guideline for respiratory management of children with neuromuscular weakness","volume":"67","author":"Hull","year":"2012","journal-title":"Thorax"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ejhg.2011.134","article-title":"Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of >72,400 specimens","volume":"20","author":"Sugarman","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","article-title":"Prevalence, incidence and carrier frequency of 5q\u2013linked spinal muscular atrophy\u2014A literature review","volume":"12","author":"Verhaart","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1093\/hmg\/7.10.1531","article-title":"The role of the SMN gene in proximal spinal muscular atrophy","volume":"7","author":"Lefebvre","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(80)90847-8","article-title":"Classification of Spinal Muscular Atrophies","volume":"315","author":"Pearn","year":"1980","journal-title":"Lancet"},{"key":"ref_6","first-page":"18","article-title":"The role of sleep diagnostics and non-invasive ventilation in children with spinal muscular atrophy","volume":"28","author":"Grychtol","year":"2018","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fmolb.2016.00007","article-title":"Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases","volume":"3","author":"Butchbach","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative Analyses of SMN1 and SMN2 Based on Real-Time LightCycler PCR: Fast and Highly Reliable Carrier Testing and Prediction of Severity of Spinal Muscular Atrophy","volume":"70","author":"Schwarzer","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1055\/s-0036-1586263","article-title":"Neuromuscular Diseases","volume":"36","author":"Morrison","year":"2016","journal-title":"Semin. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13023-020-01661-9","article-title":"Executive function is inversely correlated with physical function: The cognitive profile of adult Spinal Muscular Atrophy (SMA)","volume":"16","author":"Mix","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0883073807305788","article-title":"Consensus Statement for Standard of Care in Spinal Muscular Atrophy","volume":"22","author":"Wang","year":"2007","journal-title":"J. Child Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S245","DOI":"10.1542\/peds.2008-2952K","article-title":"Special Considerations in the Respiratory Management of Spinal Muscular Atrophy","volume":"123","author":"Schroth","year":"2009","journal-title":"Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1509-14","DOI":"10.1542\/peds.2012-2278","article-title":"Survival of Patients with Spinal Muscular Atrophy Type 1","volume":"131","author":"Gregoretti","year":"2013","journal-title":"Pediatrics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/ppul.23616","article-title":"Physician driven variation in the care of children with spinal muscular atrophy type 1: Physician Driven Variation in SMA1 Care","volume":"52","author":"Oskoui","year":"2017","journal-title":"Pediatr. Pulmonol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/labinvest.3700163","article-title":"Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients","volume":"84","author":"Arnold","year":"2004","journal-title":"Lab. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e353","DOI":"10.1212\/NXG.0000000000000353","article-title":"Impaired kidney structure and function in spinal muscular atrophy","volume":"5","author":"Nery","year":"2019","journal-title":"Neurol. Genet."},{"key":"ref_18","first-page":"932","article-title":"SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of Spinal Muscular Atrophy","volume":"26","author":"Khairallah","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bone.2015.05.039","article-title":"Bone and Spinal Muscular Atrophy","volume":"79","author":"Vai","year":"2015","journal-title":"Bone"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/PHM.0b013e31804b1d66","article-title":"Medical Considerations of Long-Term Survival of Werdnig\u2013Hoffmann Disease","volume":"86","author":"Bach","year":"2007","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pediatrneurol.2020.01.003","article-title":"Overturning the Paradigm of Spinal Muscular Atrophy as Just a Motor Neuron Disease","volume":"109","author":"Yeo","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Messina, S., and Sframeli, M. (2020). New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072222"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/MOP.0000000000000498","article-title":"Respiratory complications, management and treatments for neuromuscular disease in children","volume":"29","author":"Buu","year":"2017","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.prrv.2007.11.003","article-title":"The use of mechanical ventilation is appropriate in children with genetically proven spinal muscular atrophy type 1: The motion for","volume":"9","author":"Bach","year":"2008","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1136\/thorax.57.8.724","article-title":"Patterns and predictors of sleep disordered breathing in primary myopathies","volume":"57","author":"Ragette","year":"2002","journal-title":"Thorax"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S2213-2600(16)30151-5","article-title":"Long-term non-invasive ventilation in children","volume":"4","author":"Amaddeo","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ppul.10110","article-title":"Spinal muscular atrophy type 1: Management and outcomes","volume":"34","author":"Bach","year":"2002","journal-title":"Pediatr. Pulmonol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7S29","DOI":"10.1016\/S0929-693X(20)30274-8","article-title":"Respiratory management of children with spinal muscular atrophy (SMA)","volume":"27","author":"Fauroux","year":"2020","journal-title":"Arch. P\u00e9diatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/sleep\/34.3.389","article-title":"Executive Summary of Respiratory Indications for Polysomnography in Children: An Evidence-Based Review","volume":"34","author":"Wise","year":"2011","journal-title":"Sleep"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1183\/13993003.00385-2015","article-title":"Obstructive sleep disordered breathing in 2- to 18-year-old children: Diagnosis and management","volume":"47","author":"Kaditis","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1378\/chest.117.4.1100","article-title":"Spinal Muscular Atrophy Type 1","volume":"117","author":"Bach","year":"2000","journal-title":"Chest"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jpeds.2019.12.047","article-title":"Respiratory Needs in Patients with Type 1 Spinal Muscular Atrophy Treated with Nusinersen","volume":"219","author":"Sansone","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/00002060-200302000-00009","article-title":"Spinal Muscular Atrophy Type 1 Quality of Life","volume":"82","author":"Bach","year":"2003","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.nmd.2021.01.008","article-title":"A new respiratory scoring system for evaluation of respiratory outcomes in children with spinal muscular atrophy type1 (SMA1) on SMN enhancing drugs","volume":"31","author":"Edel","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aslesh, T., and Yokota, T. (2022). Restoring SMN Expression: An Overview of the Therapeutic Developments for the Treatment of Spinal Muscular Atrophy. Cells, 11.","DOI":"10.3390\/cells11030417"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e000572","DOI":"10.1136\/bmjpo-2019-000572","article-title":"Healthcare utilisation in children with SMA type 1 treated with Nusinersen: A single centre retrospective review","volume":"3","author":"Ali","year":"2019","journal-title":"BMJ Paediatr. Open"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/ped.13931","article-title":"Respiratory assessment in a spinal muscular atrophy infant treated with Nusinersen","volume":"61","author":"Ogawa","year":"2019","journal-title":"Pediatr. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/ana.25533","article-title":"Nusinersen in type 1 spinal muscular atrophy: Twelve-month real-world data","volume":"86","author":"Pane","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"796","DOI":"10.4103\/aian.AIAN_524_20","article-title":"Clinical Experience of Nusinersen in a Broad Spectrum of Spinal Muscular Atrophy: A Retrospective Study","volume":"23","author":"Kim","year":"2020","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/CND.0000000000000304","article-title":"Sleep and Breathing after Nusinersen Therapy in a Child with Spinal Muscular Atrophy","volume":"22","author":"Kouri","year":"2020","journal-title":"J. Clin. Neuromuscul. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1002\/acn3.51126","article-title":"Nusinersen in type 0 spinal muscular atrophy: Should we treat?","volume":"7","author":"Tiberi","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3233\/JND-200533","article-title":"Clinical Outcomes in Patients with Spinal Muscular Atrophy Type 1 Treated with Nusinersen","volume":"8","author":"Ciro","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ppul.25140","article-title":"Nusinersen for spinal muscular atrophy type 1: Real-world respiratory experience","volume":"56","author":"Lavie","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/ped.14510","article-title":"Nusinersen improved respiratory function in spinal muscular atrophy type 2","volume":"63","author":"Tanaka","year":"2021","journal-title":"Pediatr. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/acn3.51519","article-title":"Onasemnogene abeparvovec in spinal muscular atrophy: An Australian experience of safety and efficacy","volume":"9","author":"Holland","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1177\/0883073820928784","article-title":"Clinical Course in a Patient with Spinal Muscular Atrophy Type 0 Treated with Nusinersen and Onasemnogene Abeparvovec","volume":"35","author":"Matesanz","year":"2020","journal-title":"J. Child Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2352-4642(21)00287-X","article-title":"Gene replacement therapy with onasemnogene abeparvovec in children with spinal muscular atrophy aged 24 months or younger and bodyweight up to 15 kg: An observational cohort study","volume":"6","author":"Ziegler","year":"2022","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e20200729","DOI":"10.1542\/peds.2020-0729","article-title":"Gene Therapy for Spinal Muscular Atrophy: Safety and Early Outcomes","volume":"146","author":"Waldrop","year":"2020","journal-title":"Pediatrics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/ppul.24203","article-title":"Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy","volume":"54","author":"Pickard","year":"2019","journal-title":"Pediatr. Pulmonol."},{"key":"ref_51","first-page":"e1312","article-title":"Nusinersen in patients older than 7 months with spinal muscular atrophy type 1: A cohort study","volume":"91","author":"Seferian","year":"2018","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1055\/s-0042-1743439","article-title":"Parents\u2019 Perspectives on Diagnosis and Decision-Making regarding Ventilator Support in Children with SMA Type 1","volume":"53","author":"Pechmann","year":"2022","journal-title":"Neuropediatrics"},{"key":"ref_53","first-page":"54","article-title":"Real-world respiratory and bulbar comorbidities of SMA type 1 children treated with Nusinersen: 2-Year single centre Australian experience","volume":"39","author":"Chen","year":"2021","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/ppul.25135","article-title":"The respiratory impact of novel therapies for spinal muscular atrophy","volume":"56","author":"Paul","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/ana.20473","article-title":"Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function","volume":"57","author":"Swoboda","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.pediatrneurol.2015.06.002","article-title":"Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review","volume":"53","author":"Lin","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106388","DOI":"10.1016\/j.rmed.2021.106388","article-title":"Paediatric long term continuous positive airway pressure and noninvasive ventilation in France: A cross-sectional study","volume":"181","author":"Fauroux","year":"2021","journal-title":"Respir. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.sleep.2021.06.022","article-title":"Paradigm shift in the era of disease-modifying therapies for Spinal Muscular Atrophy type 1: Respiratory challenges and opportunities","volume":"86","author":"Xiao","year":"2021","journal-title":"Sleep Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/mus.27375","article-title":"Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1","volume":"64","author":"Oechsel","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/ppul.25142","article-title":"Assessment of respiratory muscles and motor function in children with SMA treated by Nusinersen","volume":"56","author":"Amaddeo","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.nmd.2017.05.011","article-title":"Spinal muscular atrophy: A changing phenotype beyond the clinical trials","volume":"27","author":"Tizzano","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1164\/rccm.201906-1175LE","article-title":"Effect of Nusinersen on Respiratory Muscle Function in Different Subtypes of Type 1 Spinal Muscular Atrophy","volume":"200","author":"LoMauro","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3233\/JND-200593","article-title":"Safety Monitoring of Gene Therapy for Spinal Muscular Atrophy with Onasemnogene Abeparvovec\u2014A Single Centre Experience","volume":"8","author":"Friese","year":"2021","journal-title":"J. Neuromuscul. 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