{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:12Z","timestamp":1753891572270,"version":"3.41.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007698","name":"University of Florida","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007698","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a rare genetic disease that results in progressive neuromuscular weakness. Without therapy, the most common form of the disease, type 1, typically results in death or chronic respiratory failure in the first 2 years of life. Thanks to the recent introduction of newborn screening programs and the discovery of three disease-modifying therapies in the last decade, the outcomes of children with SMA have dramatically improved. Patients are able to achieve many, if not all, of the typical neuromotor milestones, such as sitting, standing and walking, as well as safe oral intake. As the natural history of treated patients is continuously evolving, children with SMA continue to require complex and multidisciplinary care, posing implementation and sustainability challenges. Accordingly, there is a significant need for the application and evaluation of implementation science to address the steps involved in the diagnosis and treatment of patients with SMA, ensuring that all pertinent stakeholders and systems are working effectively to deliver timely and appropriate care. In this manuscript, we discuss the current challenges and gaps in the care for children with SMA, as well as how implementation science can advance this field. In addition, we provide an adapted implementation science framework that includes the main domains and subdomains involved in the care of patients with SMA.<\/jats:p>","DOI":"10.3389\/fneur.2022.1064194","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:32:18Z","timestamp":1670819538000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Addressing the implementation gap in advanced therapeutics for spinal muscular atrophy in the era of newborn screening programs"],"prefix":"10.3389","volume":"13","author":[{"given":"Carmen","family":"Leon-Astudillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramzi G.","family":"Salloum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/ana.25101","article-title":"Natural history of infantile-onset spinal muscular atrophy","volume":"82","author":"Kolb","year":"2017","journal-title":"Ann Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1001\/jama.2016.3867","article-title":"Convergence of implementation science, precision medicine, and the learning health care system: a new model for biomedical research","volume":"315","author":"Chambers","year":"2016","journal-title":"JAMA."},{"key":"B3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jpeds.2012.05.067","article-title":"Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy","volume":"162","author":"Farrar","year":"2013","journal-title":"J Pediatr."},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1212\/WNL.0000000000000741","article-title":"Observational study of spinal muscular atrophy type I and implications for clinical trials","volume":"83","author":"Finkel","year":"2014","journal-title":"Neurology."},{"key":"B6","doi-asserted-by":"publisher","first-page":"608249","DOI":"10.3389\/fmed.2020.608249","article-title":"Development and use of gene therapy orphan drugs-ethical needs for a broader cooperation between the pharmaceutical industry and society","volume":"7","author":"Kerpel-Fronius","year":"2020","journal-title":"Front Med (Lausanne)."},{"key":"B7","unstructured":"Office of Inspector General2022"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N Engl J Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1056\/NEJMoa2102047","article-title":"Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls","volume":"385","author":"Darras","year":"2021","journal-title":"N Engl J Med."},{"key":"B10","doi-asserted-by":"publisher","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":"B11","unstructured":"Newborn screening for SMA2022"},{"key":"B12","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3233\/JND-180304","article-title":"Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening","volume":"5","author":"Glascock","year":"2018","journal-title":"J Neuromuscul Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3390\/ijns7030033","article-title":"Landscape of Spinal muscular atrophy newborn screening in the United States: 2018\u20132021","volume":"7","author":"Hale","year":"2021","journal-title":"Int J Neonatal Screen."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390.\/ijns7020026","article-title":"Massachusetts' findings from statewide newborn screening for spinal muscular atrophy","author":"Hale","year":"2021","journal-title":"Int J Neonatal Screen 7."},{"key":"B15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13023-022-02182-3","article-title":"Patients' access to rare neuromuscular disease therapies varies across US private insurers","volume":"17","author":"Margaretos","year":"2022","journal-title":"Orphanet J Rare Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1002\/mus.27217","article-title":"Laboratory monitoring of nusinersen safety","volume":"63","author":"Goedeker","year":"2021","journal-title":"Muscle Nerve"},{"key":"B17","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/ana.24549","article-title":"Vascular defects and spinal cord hypoxia in spinal muscular atrophy","volume":"79","author":"Somers","year":"2016","journal-title":"Ann Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/mus.27363","article-title":"Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy","volume":"64","author":"Kichula","year":"2021","journal-title":"Muscle Nerve."},{"volume-title":"Systemic AAV delivery activates the classical complement pathway leading to thrombotic microangiopathy","year":"2021","author":"Salabarria","key":"B19"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1007\/s40264-021-01107-6","article-title":"Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy","volume":"44","author":"Day","year":"2021","journal-title":"Drug Saf."},{"key":"B21","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jpeds.2020.11.054","article-title":"Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: a case series","volume":"231","author":"Chand","year":"2021","journal-title":"J Pediatr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4266","DOI":"10.1182\/bloodadvances.2021006419","article-title":"Fatal thrombotic microangiopathy case following adeno-associated viral smn gene therapy","volume":"6","author":"Guillou","year":"2022","journal-title":"Blood Adv."},{"key":"B23","unstructured":"InformationEP\n          Evrysdi Prescribing Information: Important Safety Information.2020"},{"key":"B24","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/acn3.51239","article-title":"Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy","volume":"8","author":"Sergott","year":"2021","journal-title":"Ann Clin Transl Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"729","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":"B26","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/s41593-021-00827-3","article-title":"Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit","volume":"24","author":"Van Alstyne","year":"2021","journal-title":"Nat Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1089\/hum.2018.015","article-title":"Severe toxicity in nonhuman primates and piglets following high-dose intravenous administration of an adeno-associated virus vector expressing human SMN","volume":"29","author":"Hinderer","year":"2018","journal-title":"Hum Gene Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.csda.2016.09.006","article-title":"Bayesian adaptive design for clinical trials in rare diseases","volume":"113","author":"Williamson","year":"2016","journal-title":"Comput Stat Data Anal."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1080\/03007995.2021.1947216","article-title":"Matching-adjusted indirect treatment comparison of onasemnogene abeparvovec and nusinersen for the treatment of symptomatic patients with spinal muscular atrophy type 1","volume":"37","author":"Bischof","year":"2021","journal-title":"Curr Med Res Opin."},{"key":"B30","doi-asserted-by":"publisher","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":"B31","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3233\/JND-190465","article-title":"Feeding and swallowing problems in infants with spinal muscular atrophy type 1: an observational study","volume":"7","author":"van der Heul","year":"2020","journal-title":"J Neuromuscul Dis."},{"journal-title":"Inst Clin Econ Rev.","article-title":"I.f.C.a.E.R. Spinraza and Zolgensma for spinal muscular atrophy: effectivenes and value","year":"2019","key":"B32"},{"key":"B33","unstructured":"New Zolgensma Data Demonstrate Age-Appropriate Development When Used Early, Real-World Benefit in Older Children and Durability 5+ Years Post-Treatment"},{"key":"B34","unstructured":"Roche Takes on Pricey Rivals as FDA Approves SMA Drug"},{"key":"B35","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.jpeds.2020.07.033","article-title":"Cost-effectiveness of nusinersen and universal newborn screening for spinal muscular atrophy","volume":"227","author":"Jalali","year":"2020","journal-title":"J Pediatr."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2021-326344","article-title":"Newborn screening for spinal muscular atrophy with disease-modifying therapies: a cost-effectiveness analysis","author":"Shih","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B37","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13023-021-01695-7","article-title":"Systematic literature review of the economic burden of spinal muscular atrophy and economic evaluations of treatments","volume":"16","author":"Dangouloff","year":"2021","journal-title":"Orphanet J Rare Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41573-019-0049-9","article-title":"Therapies for rare diseases: therapeutic modalities, progress and challenges ahead","volume":"19","author":"Tambuyzer","year":"2020","journal-title":"Nat Rev Drug Discov."},{"key":"B39","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13012-015-0242-0","article-title":"Making sense of implementation theories, models and frameworks","volume":"10","author":"Nilsen","year":"2015","journal-title":"Implement Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/1748-5908-4-50","article-title":"Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science","volume":"4","author":"Damschroder","year":"2009","journal-title":"Implement Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.ajhg.2019.04.006","article-title":"The genomic medicine integrative research framework: a conceptual framework for conducting genomic medicine research","volume":"104","author":"Horowitz","year":"2019","journal-title":"Am J Hum Genet."},{"key":"B42","doi-asserted-by":"publisher","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":"D'Silva","year":"2022","journal-title":"Ann Clin Transl Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3389\/fpubh.2019.00064","article-title":"RE-AIM planning and evaluation framework: adapting to new science and practice with a 20-year review","volume":"7","author":"Glasgow","year":"2019","journal-title":"Front Public Health."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.1064194\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:32:22Z","timestamp":1670819542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.1064194\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":43,"alternative-id":["10.3389\/fneur.2022.1064194"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.1064194","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2022,12,12]]},"article-number":"1064194"}}