{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:31:23Z","timestamp":1793143883473,"version":"4.5.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The natural history of spinal muscular atrophy has been radically changed by the advent of improved standards of care and the availability of disease-modifying therapies. The aim of this paper is to provide the current therapeutic scenario including new perspectives and to report the challenges related to new phenotypes a few years after the therapies have become available. The paper also includes a review of real-world data that provides information on safety and efficacy in individuals that were not included in clinical trials. Special attention is paid to future perspectives both in terms of new drugs that are currently investigated in clinical trials or providing details on current developments in the use of the available drugs, including combination therapies or new modalities of dose or administration.<\/jats:p><jats:p><jats:italic>\u00a0 Conclusion<\/jats:italic>: Clinical trials and real world data support the efficacy and safety profiles of the available drugs. At the moment there is not enough published evidence about the superiority of one product compared to the others.<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td align=\"left\"><jats:bold>What is Known:<\/jats:bold><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td align=\"left\">\u2022 <jats:italic>Safety and efficacy results of clinical trials have led in the last 6\u00a0years to the marketing of three drugs for spinal muscular atrophy, with different mechanisms of action.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td align=\"left\"><jats:bold>What is New:<\/jats:bold><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td align=\"left\">\u2022 <jats:italic>Since the drug\u2019s approval, real-world data allow us to have data on bigger and heterogeneous groups of patients in contrast with those included in clinical trials.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td align=\"left\">\u2022<jats:italic> In addition to the new molecules, combinations of therapies are currently being evaluated.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-023-04883-8","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T05:02:31Z","timestamp":1681707751000},"page":"2935-2942","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["New therapies for spinal muscular atrophy: where we stand and what is next"],"prefix":"10.1007","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4753-8441","authenticated-orcid":false,"given":"Laura","family":"Antonaci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6777-1721","authenticated-orcid":false,"given":"Maria Carmela","family":"Pera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-5365","authenticated-orcid":false,"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"4883_CR1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","volume":"8","author":"E Mercuri","year":"2022","unstructured":"Mercuri E, Sumner CJ, Muntoni F, Darras BT, Finkel RS (2022) Spinal muscular atrophy. Nat Rev Dis Primers 8:52","journal-title":"Nat Rev Dis Primers"},{"key":"4883_CR2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0960-8966(91)90051-S","volume":"1","author":"V Dubowitz","year":"1991","unstructured":"Dubowitz V (1991) Chaos in classification of the spinal muscular atrophies of childhood. Neuromuscul Disord 1:77\u201380","journal-title":"Neuromuscul Disord"},{"key":"4883_CR3","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1212\/WNL.0000000000000741","volume":"83","author":"RS Finkel","year":"2014","unstructured":"Finkel RS, McDermott MP, Kaufmann P et al (2014) Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 83:810\u2013817","journal-title":"Neurology"},{"key":"4883_CR4","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/ana.25101","volume":"82","author":"SJ Kolb","year":"2017","unstructured":"Kolb SJ, Coffey CS, Yankey JW et al (2017) Natural history of infantile-onset spinal muscular atrophy. Ann Neurol 82:883\u2013891","journal-title":"Ann Neurol"},{"key":"4883_CR5","doi-asserted-by":"crossref","first-page":"e1241","DOI":"10.1212\/WNL.0000000000008166","volume":"93","author":"E Mercuri","year":"2019","unstructured":"Mercuri E, Lucibello S, Pera MC et al (2019) Long-term progression in type II spinal muscular atrophy: a retrospective observational study. Neurology 93:e1241\u2013e1247","journal-title":"Neurology"},{"key":"4883_CR6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0022-510X(96)00284-5","volume":"146","author":"K Zerres","year":"1997","unstructured":"Zerres K, Rudnik-Schoneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I (1997) 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 146:67\u201372","journal-title":"J Neurol Sci"},{"key":"4883_CR7","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1080\/13543784.2021.1904889","volume":"30","author":"L Servais","year":"2021","unstructured":"Servais L, Baranello G, Scoto M, Daron A, Oskoui M (2021) Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities. Expert Opin Investig Drugs 30:519\u2013527","journal-title":"Expert Opin Investig Drugs"},{"key":"4883_CR8","doi-asserted-by":"crossref","unstructured":"Messina S, Sframeli M (2020) New treatments in spinal muscular atrophy: positive results and new challenges. J Clin Med 9","DOI":"10.3390\/jcm9072222"},{"key":"4883_CR9","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","volume":"377","author":"JR Mendell","year":"2017","unstructured":"Mendell JR, Al-Zaidy S, Shell R et al (2017) Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 377:1713\u20131722","journal-title":"N Engl J Med"},{"key":"4883_CR10","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1001\/jamaneurol.2021.1272","volume":"78","author":"JR Mendell","year":"2021","unstructured":"Mendell JR, Al-Zaidy SA, Lehman KJ et al (2021) Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy. JAMA Neurol 78:834\u2013841","journal-title":"JAMA Neurol"},{"key":"4883_CR11","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S1474-4422(21)00001-6","volume":"20","author":"JW Day","year":"2021","unstructured":"Day JW, Finkel RS, Chiriboga CA et al (2021) Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol 20:284\u2013293","journal-title":"Lancet Neurol"},{"key":"4883_CR12","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S1474-4422(21)00251-9","volume":"20","author":"E Mercuri","year":"2021","unstructured":"Mercuri E, Muntoni F, Baranello G et al (2021) Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol 20:832\u2013841","journal-title":"Lancet Neurol"},{"key":"4883_CR13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejpn.2020.07.001","volume":"28","author":"J Kirschner","year":"2020","unstructured":"Kirschner J, Butoianu N, Goemans N et al (2020) European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy. Eur J Paediatr Neurol 28:38\u201343","journal-title":"Eur J Paediatr Neurol"},{"key":"4883_CR14","doi-asserted-by":"crossref","unstructured":"Bitetti I, Lanzara V, Margiotta G, Varone A (2022) Onasemnogene abeparvovec gene replacement therapy for the treatment of spinal muscular atrophy: a real-world observational study. Gene Ther","DOI":"10.1038\/s41434-022-00341-6"},{"key":"4883_CR15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/acn3.51519","volume":"9","author":"AM D'Silva","year":"2022","unstructured":"D\u2019Silva AM, Holland S, Kariyawasam D et al (2022) Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. Ann Clin Transl Neurol 9:339\u2013350","journal-title":"Ann Clin Transl Neurol"},{"key":"4883_CR16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pediatrneurol.2021.01.012","volume":"118","author":"SE Matesanz","year":"2021","unstructured":"Matesanz SE, Battista V, Flickinger J, Jones JN, Kichula EA (2021) Clinical experience with gene therapy in older patients with spinal muscular atrophy. Pediatr Neurol 118:1\u20135","journal-title":"Pediatr Neurol"},{"key":"4883_CR17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2352-4642(21)00287-X","volume":"6","author":"C Weiss","year":"2022","unstructured":"Weiss C, Ziegler A, Becker LL et al (2022) 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. Lancet Child Adolesc Health 6:17\u201327","journal-title":"Lancet Child Adolesc Health"},{"key":"4883_CR18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jhep.2020.11.001","volume":"74","author":"D Chand","year":"2021","unstructured":"Chand D, Mohr F, McMillan H et al (2021) Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy. J Hepatol 74:560\u2013566","journal-title":"J Hepatol"},{"key":"4883_CR19","doi-asserted-by":"crossref","unstructured":"Chand DH, Mitchell S, Sun R, LaMarca N, Reyna SP, Sutter T (2022) Safety of onasemnogene abeparvovec for patients with spinal muscular atrophy 8.5 kg or heavier in a global managed access program. Pediatr Neurol 132:27\u201332","DOI":"10.1016\/j.pediatrneurol.2022.05.001"},{"key":"4883_CR20","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.braindev.2021.12.006","volume":"44","author":"S Lee","year":"2022","unstructured":"Lee S, Lee YJ, Kong J et al (2022) Short-term clinical outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy. Brain Dev 44:287\u2013293","journal-title":"Brain Dev"},{"key":"4883_CR21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jpeds.2020.11.054","volume":"231","author":"DH Chand","year":"2021","unstructured":"Chand DH, Zaidman C, Arya K et al (2021) Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: a case series. J Pediatr 231:265\u2013268","journal-title":"J Pediatr"},{"key":"4883_CR22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S2352-4642(21)00100-0","volume":"5","author":"RS Finkel","year":"2021","unstructured":"Finkel RS, Chiriboga CA, Vajsar J et al (2021) Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study. Lancet Child Adolesc Health 5:491\u2013500","journal-title":"Lancet Child Adolesc Health"},{"key":"4883_CR23","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","volume":"377","author":"RS Finkel","year":"2017","unstructured":"Finkel RS, Mercuri E, Darras BT et al (2017) Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med 377:1723\u20131732","journal-title":"N Engl J Med"},{"key":"4883_CR24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","volume":"378","author":"E Mercuri","year":"2018","unstructured":"Mercuri E, Darras BT, Chiriboga CA et al (2018) Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 378:625\u2013635","journal-title":"N Engl J Med"},{"key":"4883_CR25","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1212\/WNL.0000000000002445","volume":"86","author":"CA Chiriboga","year":"2016","unstructured":"Chiriboga CA, Swoboda KJ, Darras BT et al (2016) Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 86:890\u2013897","journal-title":"Neurology"},{"key":"4883_CR26","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","volume":"388","author":"RS Finkel","year":"2016","unstructured":"Finkel RS, Chiriboga CA, Vajsar J et al (2016) Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 388:3017\u20133026","journal-title":"Lancet"},{"key":"4883_CR27","doi-asserted-by":"crossref","first-page":"e1312","DOI":"10.1212\/WNL.0000000000006281","volume":"91","author":"K Aragon-Gawinska","year":"2018","unstructured":"Aragon-Gawinska K, Seferian AM, Daron A et al (2018) Nusinersen in patients older than 7 months with spinal muscular atrophy type 1: a cohort study. Neurology 91:e1312\u2013e1318","journal-title":"Neurology"},{"key":"4883_CR28","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/ana.25533","volume":"86","author":"M Pane","year":"2019","unstructured":"Pane M, Coratti G, Sansone VA et al (2019) Nusinersen in type 1 spinal muscular atrophy: twelve-month real-world data. Ann Neurol 86:443\u2013451","journal-title":"Ann Neurol"},{"key":"4883_CR29","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","volume":"19","author":"T Hagenacker","year":"2020","unstructured":"Hagenacker T, Wurster CD, Gunther R et al (2020) Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol 19:317\u2013325","journal-title":"Lancet Neurol"},{"key":"4883_CR30","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/dmcn.14412","volume":"62","author":"K Aragon-Gawinska","year":"2020","unstructured":"Aragon-Gawinska K, Daron A, Ulinici A et al (2020) Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen. Dev Med Child Neurol 62:310\u2013314","journal-title":"Dev Med Child Neurol"},{"key":"4883_CR31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3233\/JND-190441","volume":"7","author":"A Pechmann","year":"2020","unstructured":"Pechmann A, Baumann M, Bernert G et al (2020) Treatment with nusinersen - challenges Regarding the Indication for Children with SMA Type 1. J Neuromuscul Dis 7:41\u201346","journal-title":"J Neuromuscul Dis"},{"key":"4883_CR32","unstructured":"Pechmann A, Behrens M, Dornbrack K et al (2022) Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy. Brain"},{"key":"4883_CR33","doi-asserted-by":"crossref","unstructured":"Sansone VA, Pirola A, Albamonte E et al (2020) Respiratory needs in patients with type 1 spinal muscular atrophy treated with nusinersen. J Pediatr","DOI":"10.1016\/j.jpeds.2019.12.047"},{"key":"4883_CR34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/acn3.51514","volume":"9","author":"M Pane","year":"2022","unstructured":"Pane M, Coratti G, Pera MC et al (2022) Nusinersen efficacy data for 24-month in type 2 and 3 spinal muscular atrophy. Ann Clin Transl Neurol 9:404\u2013409","journal-title":"Ann Clin Transl Neurol"},{"key":"4883_CR35","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.nmd.2021.03.012","volume":"31","author":"G Coratti","year":"2021","unstructured":"Coratti G, Pane M, Lucibello S et al (2021) Age related treatment effect in type II spinal muscular atrophy pediatric patients treated with nusinersen. Neuromuscul Disord 31:596\u2013602","journal-title":"Neuromuscul Disord"},{"key":"4883_CR36","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1002\/acn3.51411","volume":"8","author":"MC Pera","year":"2021","unstructured":"Pera MC, Coratti G, Bovis F et al (2021) Nusinersen in pediatric and adult patients with type III spinal muscular atrophy. Ann Clin Transl Neurol 8:1622\u20131634","journal-title":"Ann Clin Transl Neurol"},{"key":"4883_CR37","doi-asserted-by":"crossref","unstructured":"Sansone VA, Coratti G, Pera MC et al (2020) Sometimes they come back: new and old spinal muscular atrophy adults in the era of nusinersen. Eur J Neurol","DOI":"10.1111\/ene.14567"},{"key":"4883_CR38","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3233\/JND-200551","volume":"8","author":"RH Mendonca","year":"2021","unstructured":"Mendonca RH, Polido GJ, Matsui C et al (2021) Real-world data from nusinersen treatment for patients with later-onset spinal muscular atrophy: a single center experience. J Neuromuscul Dis 8:101\u2013108","journal-title":"J Neuromuscul Dis"},{"key":"4883_CR39","unstructured":"ed. Pharmacoeconomic review report: nusinersen (Spinraza): (Biogen Canada Inc.): indication: treatment of patients with 5q SMA. Ottawa (ON), 2018"},{"key":"4883_CR40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13023-020-01414-8","volume":"15","author":"F Audic","year":"2020","unstructured":"Audic F, de la Banda MGG, Bernoux D et al (2020) Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study. Orphanet J Rare Dis 15:148","journal-title":"Orphanet J Rare Dis"},{"key":"4883_CR41","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1136\/jnnp-2020-324532","volume":"92","author":"SH Chan","year":"2021","unstructured":"Chan SH, Chae JH, Chien YH et al (2021) Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions. J Neurol Neurosurg Psychiatry 92:1244\u20131246","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"4883_CR42","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00415-020-10223-9","volume":"268","author":"B De Wel","year":"2021","unstructured":"De Wel B, Goosens V, Sobota A et al (2021) Nusinersen treatment significantly improves hand grip strength, hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4. J Neurol 268:923\u2013935","journal-title":"J Neurol"},{"key":"4883_CR43","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1212\/CPJ.0000000000001033","volume":"11","author":"T Duong","year":"2021","unstructured":"Duong T, Wolford C, McDermott MP et al (2021) Nusinersen treatment in adults with spinal muscular atrophy. Neurol Clin Pract 11:e317\u2013e327","journal-title":"Neurol Clin Pract"},{"key":"4883_CR44","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1136\/jnnp-2020-323822","volume":"91","author":"L Maggi","year":"2020","unstructured":"Maggi L, Bello L, Bonanno S et al (2020) Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. J Neurol Neurosurg Psychiatry 91:1166\u20131174","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"4883_CR45","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/s13023-021-02065-z","volume":"16","author":"G Coratti","year":"2021","unstructured":"Coratti G, Cutrona C, Pera MC et al (2021) Motor function in type 2 and 3 SMA patients treated with nusinersen: a critical review and meta-analysis. Orphanet J Rare Dis 16:430","journal-title":"Orphanet J Rare Dis"},{"key":"4883_CR46","doi-asserted-by":"crossref","unstructured":"Scheijmans FEV, Cuppen I, van Eijk RPA et al (2022) Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study. Brain Commun 4:fcac269","DOI":"10.1093\/braincomms\/fcac269"},{"key":"4883_CR47","doi-asserted-by":"crossref","first-page":"6501","DOI":"10.1021\/acs.jmedchem.8b00741","volume":"61","author":"H Ratni","year":"2018","unstructured":"Ratni H, Ebeling M, Baird J et al (2018) Discovery of risdiplam, a selective survival of motor neuron-2 ( SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J Med Chem 61:6501\u20136517","journal-title":"J Med Chem"},{"key":"4883_CR48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/bcp.13786","volume":"85","author":"S Sturm","year":"2019","unstructured":"Sturm S, Gunther A, Jaber B et al (2019) A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br J Clin Pharmacol 85:181\u2013193","journal-title":"Br J Clin Pharmacol"},{"key":"4883_CR49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa2102047","volume":"385","author":"BT Darras","year":"2021","unstructured":"Darras BT, Masson R, Mazurkiewicz-Beldzinska M et al (2021) Risdiplam-treated infants with type 1 spinal muscular atrophy versus historical controls. N Engl J Med 385:427\u2013435","journal-title":"N Engl J Med"},{"key":"4883_CR50","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1056\/NEJMoa2009965","volume":"384","author":"G Baranello","year":"2021","unstructured":"Baranello G, Darras BT, Day JW et al (2021) Risdiplam in type 1 spinal muscular atrophy. N Engl J Med 384:915\u2013923","journal-title":"N Engl J Med"},{"key":"4883_CR51","unstructured":"Masson R, Mazurkiewicz-Be\u0142dzi\u0144ska, Rose, K, Servais, L, Xiong, H, Darras, BT (2022) Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet neurology. in press"},{"key":"4883_CR52","doi-asserted-by":"crossref","unstructured":"Mercuri E, Baranello G, Boespflug-Tanguy O et al (2022) Risdiplam in types 2 and 3 spinal muscular atrophy: a randomised, placebo-controlled, dose-finding trial followed by 24 months of treatment. Eur J Neurol","DOI":"10.1111\/ene.15499"},{"key":"4883_CR53","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1474-4422(21)00367-7","volume":"21","author":"E Mercuri","year":"2022","unstructured":"Mercuri E, Deconinck N, Mazzone ES et al (2022) Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol 21 42 52","journal-title":"Lancet Neurol"},{"key":"4883_CR54","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1038\/s41598-018-20524-9","volume":"8","author":"M Pirruccello-Straub","year":"2018","unstructured":"Pirruccello-Straub M, Jackson J, Wawersik S\u00a0et al\u00a0(2018) Blocking extracellular activation of myostatin as a strategy for treating muscle wasting Sci Rep 8:2292","journal-title":"Sci Rep"},{"key":"4883_CR55","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1007\/s12325-021-01757-z","volume":"38","author":"D Barrett","year":"2021","unstructured":"Barrett D, Bilic S, Chyung Y\u00a0et al\u00a0(2021) A randomized phase 1 safety, pharmacokinetic and pharmacodynamic study of the novel myostatin inhibitor apitegromab (SRK-015): a potential treatment for spinal muscular atrophy. Adv Ther 38:3203\u20133222","journal-title":"Adv Ther"},{"key":"4883_CR56","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1212\/WNL.0b013e3182749eca","volume":"79","author":"RI Wadman","year":"2012","unstructured":"Wadman RI, Vrancken AF, van den Berg LH, van der Pol WL (2012) Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3. Neurology 79:2050\u20135","journal-title":"Neurology"},{"key":"4883_CR57","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.nmd.2017.07.007","volume":"27","author":"MC Pera","year":"2017","unstructured":"Pera MC, Luigetti M, Pane M et al (2017) 6MWT can identify type 3 SMA patients with neuromuscular junction dysfunction. Neuromuscul Disord 27:879\u2013882","journal-title":"Neuromuscul Disord"},{"key":"4883_CR58","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1212\/WNL.0b013e3181d3e308","volume":"74","author":"J Montes","year":"2010","unstructured":"Montes J, McDermott MP, Martens WB et al (2010) Six-minute walk test demonstrates motor fatigue in spinal muscular atrophy. Neurology 74:833\u20138","journal-title":"Neurology"},{"key":"4883_CR59","volume":"13","author":"J Montes","year":"2018","unstructured":"Montes J, McDermott MP, Mirek E et al (2018) Ambulatory function in spinal muscular atrophy: age-related patterns of progression. PLoS One 13 e0199657","journal-title":"PLoS One"},{"key":"4883_CR60","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1212\/WNL.59.4.609","volume":"59","author":"M Kinali","year":"2002","unstructured":"Kinali M, Mercuri E, Main M et al (2002) Pilot trial of albuterol in spinal muscular atrophy. Neurology 59:609\u201310","journal-title":"Neurology"},{"key":"4883_CR61","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.nmd.2008.05.004","volume":"18","author":"M Pane","year":"2008","unstructured":"Pane M, Staccioli S, Messina S et al (2008) Daily salbutamol in young patients with SMA type II. Neuromuscul Disord 18:536\u201340","journal-title":"Neuromuscul Disord"},{"key":"4883_CR62","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.nmd.2018.07.013","volume":"28","author":"MC Pera","year":"2018","unstructured":"Pera MC, Luigetti M, Sivo S et al (2018) Does albuterol have an effect on neuromuscular junction dysfunction in spinal muscular atrophy? Neuromuscul Disord 28:863\u2013864","journal-title":"Neuromuscul Disord"},{"key":"4883_CR63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.nmd.2017.11.004","volume":"28","author":"RS Finkel","year":"2018","unstructured":"Finkel RS, Mercuri E, Meyer OH et al (2018) Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 28:197\u2013207","journal-title":"Neuromuscul Disord"},{"key":"4883_CR64","unstructured":"Mercuri E, Finkel RS, Muntoni F et al (2017) Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord"},{"key":"4883_CR65","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2017-019932","volume":"8","author":"M Stam","year":"2018","unstructured":"Stam M, Wadman RI, Wijngaarde CA et al (2018) Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2\u20134 (SPACE trial). BMJ Open 8:e019932","journal-title":"BMJ Open"},{"key":"4883_CR66","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","volume":"29","author":"DC De Vivo","year":"2019","unstructured":"De Vivo DC, Bertini E, Swoboda KJ et al (2019) 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 29:842856","journal-title":"Neuromuscul Disord"},{"key":"4883_CR67","doi-asserted-by":"crossref","unstructured":"Strauss KA, Farrar MA, Muntoni F et al (2022) Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial. Nat Med\u00a0","DOI":"10.1038\/s41591-022-01866-4"},{"key":"4883_CR68","doi-asserted-by":"crossref","unstructured":"Strauss KA, Farrar MA, Muntoni F et al (2022) Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat Med","DOI":"10.1038\/s41591-022-01867-3"},{"key":"4883_CR69","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3233\/JND-200614","volume":"8","author":"B Berti","year":"2021","unstructured":"Berti B, Fanelli L, de Sanctis R et al (2021) Oral and swallowing abilities tool (OrSAT) for type 1 sma patients: development of a new module. J Neuromuscul Dis 8:589\u2013601","journal-title":"J Neuromuscul Dis"},{"key":"4883_CR70","doi-asserted-by":"crossref","unstructured":"Berti B, Fanelli L, Stanca G et al (2022) Oral and swallowing abilities tool (OrSAT) in nusinersen treated patients. Arch Dis Child","DOI":"10.1136\/archdischild-2022-323899"},{"key":"4883_CR71","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1136\/thoraxjnl-2020-216564","volume":"77","author":"A Chacko","year":"2022","unstructured":"Chacko A, Sly PD, Ware RS et al (2022) Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1\u20133. Thorax 77:40\u201346","journal-title":"Thorax"},{"key":"4883_CR72","first-page":"54","volume":"39","author":"KA Chen","year":"2021","unstructured":"Chen KA, Widger J, Teng A, Fitzgerald DA, D'Silva A, Farrar M (2021) Real-world respiratory and bulbar comorbidities of SMA type 1 children treated with nusinersen: 2-year single centre Australian experience. Paediatr Respir Rev 39:54\u201360","journal-title":"Paediatr Respir Rev"},{"key":"4883_CR73","doi-asserted-by":"crossref","first-page":"e587","DOI":"10.1212\/WNL.0000000000011051","volume":"96","author":"F Trucco","year":"2021","unstructured":"Trucco F, Ridout D, Scoto M et al (2021) Respiratory trajectories in type 2 and 3 spinal muscular atrophy in the iSMAC cohort study. Neurology 96:e587\u2013e599","journal-title":"Neurology"},{"key":"4883_CR74","doi-asserted-by":"crossref","unstructured":"Darras BT, Crawford TO, Finkel RS, Mercuri E, De Vivo DC, Oskoui M, Eduardo T et al (2019) Neurofilament as a potential biomarker for spinal muscular atrophy. Ann Clin Transl Neurol","DOI":"10.1002\/acn3.779"},{"key":"4883_CR75","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s00415-019-09646-w","volume":"267","author":"C Brogna","year":"2020","unstructured":"Brogna C, Cristiano L, Verdolotti T et al (2020) MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients. J Neurol 267:898\u2013912","journal-title":"J Neurol"},{"key":"4883_CR76","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.nmd.2021.03.007","volume":"31","author":"Dangouloff T, Vrscaj E, Servais L, Osredkar D, Group SNWS","year":"2021","unstructured":"Dangouloff T, Vrscaj E, Servais L, Osredkar D, Group SNWS (2021) Newborn screening programs for spinal muscular atrophy worldwide: where we stand and where to go. Neuromuscul Disord 31:574\u2013582","journal-title":"Neuromuscul Disord"},{"key":"4883_CR77","doi-asserted-by":"publisher","unstructured":"Coratti G, Lenkowicz J, Patarnello S, Gull\u00ec C, Pera MC, Masciocchi C, Rinaldi R, Lovato V, Leone A, Cesario A, Mercuri E (2022) Predictive models in SMA II natural history trajectories using machine learning: a proof of concept study. PLoS One 17(5):e0267930. https:\/\/doi.org\/10.1371\/journal.pone.0267930. PMID: 35511762; PMCID: PMC9070873","DOI":"10.1371\/journal.pone.0267930"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-023-04883-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-023-04883-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-023-04883-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T13:04:28Z","timestamp":1689685468000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-023-04883-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":77,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["4883"],"URL":"https:\/\/doi.org\/10.1007\/s00431-023-04883-8","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]},"assertion":[{"value":"23 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the institutional review board (ethics committee) of Fondazione Policlinico Universitario Agostino Gemelli, as the coordinator center (N. 0030504\/18).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}