[en] Spinal muscular atrophy (SMA) is a rare neurodegenerative neuromuscular disorder with a wide phenotypic spectrum of severity. SMA was previously life limiting for patients with the most severe phenotype and resulted in progressive disability for those with less severe phenotypes. This has changed dramatically in the past few years with the approvals of three disease-modifying treatments. We review the evidence supporting the use of currently approved SMA treatments (nusinersen, onasemnogene abeparvovec, and risdiplam), focusing on mechanisms of action, side effect profiles, published clinical trial data, health economics, and pending questions. Whilst there is robust data from clinical trials of efficacy and side effect profile for individual drugs in select SMA populations, there are no comparative head-to-head clinical trials. This presents a challenge for clinicians who need to make recommendations on the best treatment option for an individual patient and we hope to provide a pragmatic approach for clinicians across each SMA profile based on current evidence.
Disciplines :
Pediatrics
Author, co-author :
Ramdas, Sithara; Department of Paediatrics, MDUK Oxford Neuromuscular Centre and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK ; Department of Paediatric Neurology, John Radcliffe Hospital, Oxford, UK
Oskoui, Maryam; Departments of Pediatrics and Neurology and Neurosurgery, McGill University, Montreal, Canada ; Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; Department of Paediatrics, MDUK Oxford Neuromuscular Centre and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Laurent.servais@paediatrics.ox.ac.uk ; Academic Paediatric Department, Level 2 Children Hospital-John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK. Laurent.servais@paediatrics.ox.ac.uk
Language :
English
Title :
Treatment Options in Spinal Muscular Atrophy: A Pragmatic Approach for Clinicians.
I.E.C. Verhaart A. Robertson I.J. Wilson A. Aartsma-Rus S. Cameron C.C. Jones et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy—a literature review Orphanet J Rare Dis 2017 12 1 124 10.1186/s13023-017-0671-8 28676062 5496354 Epub 20170704. PubMed PMID: 28676062; PubMed Central PMCID: PMCPMC5496354
P.E. McAndrew D.W. Parsons L.R. Simard C. Rochette P.N. Ray J.R. Mendell et al. Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number Am J Hum Genet 1997 60 6 1411 1422 1:CAS:528:DyaK2sXktlOqtbs%3D 10.1086/515465 9199562 1716150 PubMed PMID: 9199562; PubMed CentralPMCID: PMCPMC1716150
K. Aragon-Gawinska C. Mouraux T. Dangouloff L. Servais Spinal muscular atrophy treatment in patients identified by newborn screening-a systematic review Genes (Basel). 2023 10.3390/genes14071377 37510282 10379202 Epub 20230629. PubMed PMID: 37510282; PubMed Central PMCID: PMCPMC10379202
S. Lefebvre L. Bürglen S. Reboullet O. Clermont P. Burlet L. Viollet et al. Identification and characterization of a spinal muscular atrophy-determining gene Cell 1995 80 1 155 165 1:CAS:528:DyaK2MXjtFegu74%3D 10.1016/0092-8674(95)90460-3 7813012 PubMed PMID: 7813012
B. Wirth 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 1:CAS:528:DC%2BD3cXitVGjtr0%3D 10.1002/(sici)1098-1004(200003)15:3<228::Aid-humu3>3.0.Co;2-9 10679938 PubMed PMID: 10679938
M. Calucho S. Bernal L. Alías F. March A. Venceslá F.J. Rodríguez-Álvarez et al. Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases Neuromuscul Disord 2018 28 3 208 215 10.1016/j.nmd.2018.01.003 29433793 Epub 20180111. PubMed PMID: 29433793
B. Wirth N. Mendoza-Ferreira L. Torres-Benito Spinal muscular atrophy disease modifiers. Spinal muscular atrophy 2017 Amsterdam Elsevier 191 210 10.1016/B978-0-12-803685-3.00012-4
T.W. Prior A.R. Krainer Y. Hua K.J. Swoboda P.C. Snyder S.J. Bridgeman et al. A positive modifier of spinal muscular atrophy in the SMN2 gene Am J Hum Genet 2009 85 3 408 413 1:CAS:528:DC%2BD1MXhsVChsL%2FM 10.1016/j.ajhg.2009.08.002 19716110 2771537
TL M. International SMA consortium meeting. (26–28 June 1992, Bonn, Germany). Neuromuscul Disord. 1992;2:423–8.
Polido GJ, Miranda MMVd, Carvas N, Mendonça RdH, Caromano FA, Reed UC, et al. Cognitive performance of children with spinal muscular atrophy: a systematic review. Dementia Neuropsychologia. 2019;13:436–43.
M. Ngawa F. Dal Farra A.-D. Marinescu L. Servais Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy Ther Adv Neurol Disord 2023 16 17562864231154335 10.1177/17562864231154335 36846472 9944336
R. Masson C. Brusa M. Scoto G. Baranello Brain, cognition, and language development in spinal muscular atrophy type 1: a scoping review Dev Med Child Neurol 2021 63 5 527 536 10.1111/dmcn.14798 33452688
Baranello G, Group NiSW. The emerging spectrum of neurodevelopmental comorbidities in early-onset spinal muscular atrophy. Eur J Paediatr Neurol. 2023;48:67–8. https://doi.org/10.1016/j.ejpn.2023.11.006(Epub 20231123. PubMed PMID: 38043384).
E. Mercuri R.S. Finkel F. Muntoni B. Wirth J. Montes M. Main et al. Diagnosis and management of spinal muscular atrophy: Part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care Neuromuscul Disord 2018 28 2 103 115 10.1016/j.nmd.2017.11.005 29290580
R.S. Finkel E. Mercuri O.H. Meyer A.K. Simonds M.K. Schroth R.J. Graham et al. Diagnosis and management of spinal muscular atrophy: Part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics Neuromuscul Disord 2018 28 3 197 207 10.1016/j.nmd.2017.11.004 29305137 Epub 20171123. PubMed PMID: 29305137
D.J. Birnkrant K. Bushby C.M. Bann S.D. Apkon A. Blackwell M.K. Colvin et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan Lancet Neurol 2018 17 5 445 455 10.1016/S1474-4422(18)30026-7 29398641 5902408
S.M. Hoy Nusinersen: first global approval Drugs 2017 77 473 479 1:CAS:528:DC%2BC2sXjsFCqurk%3D 10.1007/s40265-017-0711-7 28229309
R.S. Finkel C.A. Chiriboga J. Vajsar J.W. Day J. Montes D.C. De Vivo et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study Lancet 2016 388 10063 3017 3026 1:CAS:528:DC%2BC28XitVegurfO 10.1016/S0140-6736(16)31408-8 27939059 Epub 20161207. PubMed PMID: 27939059
G. Acsadi T.O. Crawford W. Müller-Felber P.B. Shieh R. Richardson N. Natarajan et al. Safety and efficacy of nusinersen in spinal muscular atrophy: the EMBRACE study Muscle Nerve 2021 63 5 668 677 1:CAS:528:DC%2BB3MXpt12hsbc%3D 10.1002/mus.27187 33501671 8248061 Epub 20210216. PubMed PMID: 33501671; PubMed Central PMCID: PMCPMC8248061
E. Mercuri B.T. Darras C.A. Chiriboga J.W. Day C. Campbell A.M. Connolly et al. Nusinersen versus sham control in later-onset spinal muscular atrophy N Engl J Med 2018 378 7 625 635 1:CAS:528:DC%2BC1cXktFClsr0%3D 10.1056/NEJMoa1710504 29443664 PubMed PMID: 29443664
E. Viscidi N. Wang M. Juneja I. Bhan C. Prada D. James et al. The incidence of hydrocephalus among patients with and without spinal muscular atrophy (SMA): results from a US electronic health records study Orphanet J Rare Dis 2021 16 1 207 10.1186/s13023-021-01822-4 33962637 8105953 Epub 20210507. PubMed PMID: 33962637; PubMed Central PMCID: PMCPMC8105953
G. Machetanz M. Grziwotz L. Semmler M. Maier C. Maegerlein M. Deschauer Symptomatic intracranial hypertension in an adult patient with spinal muscular atrophy and arachnoid cysts receiving nusinersen J Neuromuscul Dis. 2023 10 4 719 725 10.3233/JND-230032 37248913 10357201 PubMed PMID: 37248913; PubMed Central PMCID: PMCPMC10357201
F.E.V. Scheijmans I. Cuppen M.M. Zwartkruis I. Signoria C. van Ekris F. Asselman et al. Inflammatory markers in cerebrospinal fluid of paediatric spinal muscular atrophy patients receiving nusinersen treatment Eur J Paediatr Neurol 2023 42 34 41 1:CAS:528:DC%2BB38XjtFaisbfK 10.1016/j.ejpn.2022.12.003 36525882 Epub 20221207. PubMed PMID: 36525882
J. Ubysz M. Koszewicz J. Bladowska S. Budrewicz Spinal adhesive arachnoiditis in an adult patient with spinal muscular atrophy type 3 treated with intrathecal therapy BMC Neurol 2024 24 1 43 10.1186/s12883-024-03543-0 38267835 10807066 Epub 20240124. PubMed PMID: 38267835; PubMed Central PMCID: PMCPMC10807066
M. Oskoui L. Servais Spinal muscular atrophy Continuum (Minneap Minn). 2023 29 5 1564 1584 10.1212/CON.0000000000001338 37851043 PubMed PMID: 37851043
label E. Nusinsersen EMA label 2023 [cited 2024 11/02/2024]. https://www.ema.europa.eu/en/medicines/human/EPAR/spinraza. Accessed 11/2/2024.
T. Markati G. Fisher S. Ramdas L. Servais Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA) Expert Opin Investig Drugs 2022 31 5 451 461 1:CAS:528:DC%2BB38XpsV2ns7c%3D 10.1080/13543784.2022.2056836 35316106 Epub 20220411. PubMed PMID: 35316106
Label E. Risdiplam 2024 [cited 2024 11/02/2024]. https://www.ema.europa.eu/en/medicines/human/EPAR/evrysdi. Accessed 11/2/2024.
G. Baranello B.T. Darras J.W. Day N. Deconinck A. Klein R. Masson et al. Risdiplam in type 1 spinal muscular atrophy N Engl J Med 2021 384 10 915 923 1:CAS:528:DC%2BB3MXmsV2rtL0%3D 10.1056/NEJMoa2009965 33626251 Epub 20210224. PubMed PMID: 33626251
B.T. Darras R. Masson M. Mazurkiewicz-Bełdzińska K. Rose H. Xiong E. Zanoteli et al. Risdiplam-treated infants with type 1 spinal muscular atrophy versus historical controls N Engl J Med 2021 385 5 427 435 1:CAS:528:DC%2BB3MXhslaisrnO 10.1056/NEJMoa2102047 34320287 PubMed PMID: 34320287
L. Mueller P. Barrow B. Jacobsen M. Ebeling G. Weinbauer Reproductive findings in male animals exposed to selective survival of motor neuron 2 (SMN2) gene splicing-modifying agents Reprod Toxicol 2023 118 1:CAS:528:DC%2BB3sXmsFSqsLg%3D 10.1016/j.reprotox.2023.108360 36894038
H.A. Blair Onasemnogene Abeparvovec: a review in spinal muscular atrophy CNS Drugs 2022 36 9 995 1005 10.1007/s40263-022-00941-1 35960489
D.H. Chand S. Mitchell R. Sun N. LaMarca S.P. Reyna T. Sutter Safety of onasemnogene abeparvovec for patients with spinal muscular atrophy 8.5 kg or heavier in a global managed access program Pediatr Neurol 2022 132 27 32 10.1016/j.pediatrneurol.2022.05.001 35605311 Epub 20220510. PubMed PMID: 35605311
L. Servais J.W. Day D.C. De Vivo J. Kirschner E. Mercuri F. Muntoni et al. Real-world outcomes in patients with spinal muscular atrophy treated with onasemnogene abeparvovec monotherapy: findings from the RESTORE registry J Neuromuscul Dis. 2024 10.3233/JND-230122 38943396 10977451 Epub 20240118. PubMed PMID: 38250783
D. Yang Y. Ruan Y. Chen Safety and efficacy of gene therapy with onasemnogene abeparvovec in the treatment of spinal muscular atrophy: a systematic review and meta-analysis J Paediatr Child Health 2023 59 3 431 438 1:CAS:528:DC%2BB3sXhsFOjsr%2FI 10.1111/jpc.16340 36722610 Epub 20230201. PubMed PMID: 36722610
W. Zhuang M. Lu Y. Wu Z. Chen M. Wang X. Wang et al. Safety concerns with nusinersen, risdiplam, and onasemnogene abeparvovec in spinal muscular atrophy: a real-world pharmacovigilance study Clin Drug Investig 2023 43 12 949 962 1:CAS:528:DC%2BB3sXisFGis7%2FM 10.1007/s40261-023-01320-4 37995087 Epub 20231123. PubMed PMID: 37995087
J.W. Day J.R. Mendell E. Mercuri R.S. Finkel K.A. Strauss A. Kleyn et al. Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy Drug Saf 2021 44 10 1109 1119 1:CAS:528:DC%2BB3MXit1KhsL7P 10.1007/s40264-021-01107-6 34383289 8473343 Epub 20210812. PubMed PMID: 34383289; PubMed Central PMCID: PMCPMC8473343
C. Weiß A. Ziegler L.L. Becker J. Johannsen H. Brennenstuhl G. Schreiber et al. 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. 2022 6 1 17 27 10.1016/S2352-4642(21)00287-X 34756190 Epub 20211029. PubMed PMID: 34756190
Gowda V, Atherton M, Murugan A, Servais L, Sheehan J, Standing E, et al. Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom. Lancet Regional Health Europe. 2024;37.
D.H. Chand C. Zaidman K. Arya R. Millner M.A. Farrar F.E. Mackie et al. Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: a case series J Pediatr 2021 231 265 268 1:CAS:528:DC%2BB3MXitlGnt78%3D 10.1016/j.jpeds.2020.11.054 33259859
J. Guillou A. de Pellegars F. Porcheret V. Frémeaux-Bacchi E. Allain-Launay C. Debord et al. Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy Blood Adv 2022 6 14 4266 4270 1:CAS:528:DC%2BB38XitlCrsLzK 10.1182/bloodadvances.2021006419 35584395 9327533 PubMed PMID: 35584395; PubMed Central PMCID: PMCPMC9327533
J.W. Day R.S. Finkel C.A. Chiriboga A.M. Connolly T.O. Crawford B.T. Darras et al. 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 2021 20 4 284 293 1:CAS:528:DC%2BB3MXhtVOmtbvL 10.1016/S1474-4422(21)00001-6 33743238 Epub 20210317. PubMed PMID: 33743238
E. Abiusi A. Vaisfeld S. Fiori A. Novelli S. Spartano M.V. Faggiano et al. Experience of a 2-year spinal muscular atrophy NBS pilot study in Italy: towards specific guidelines and standard operating procedures for the molecular diagnosis J Med Genet 2023 60 7 697 705 1:CAS:528:DC%2BB2cXhtFGns7g%3D 10.1136/jmg-2022-108873 36414255 Epub 20221122. PubMed PMID: 36414255
E. Mercuri G. Baranello O. Boespflug-Tanguy L. De Waele N. Goemans J. Kirschner et al. 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 2023 30 7 1945 1956 10.1111/ene.15499 35837793 Epub 20220801. PubMed PMID: 35837793
E. Mercuri N. Deconinck E.S. Mazzone A. Nascimento M. Oskoui K. Saito et al. 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 2022 21 1 42 52 1:CAS:528:DC%2BB38XhtVantbvL 10.1016/S1474-4422(21)00367-7 34942136 PubMed PMID: 34942136
M. Oskoui J.W. Day N. Deconinck E.S. Mazzone A. Nascimento K. Saito et al. Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA) J Neurol 2023 270 5 2531 2546 1:CAS:528:DC%2BB3sXivFSrurg%3D 10.1007/s00415-023-11560-1 36735057 9897618 Epub 20230203. PubMed PMID: 36735057; PubMed Central PMCID: PMCPMC9897618
T. Dangouloff M. Hiligsmann N. Deconinck A. D'Amico A.M. Seferian F. Boemer et al. Financial cost and quality of life of patients with spinal muscular atrophy identified by symptoms or newborn screening Dev Med Child Neurol 2023 65 1 67 77 10.1111/dmcn.15286 35673937 Epub 20220608. PubMed PMID: 35673937
T.O. Crawford K.J. Swoboda D.C. De Vivo E. Bertini W.L. Hwu R.S. Finkel et al. Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study Muscle Nerve 2023 68 2 157 170 1:CAS:528:DC%2BB3sXhsVegtrnF 10.1002/mus.27853 37409780 Epub 20230706. PubMed PMID: 37409780
K.A. Strauss M.A. Farrar F. Muntoni K. Saito J.R. Mendell L. Servais et al. 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 2022 28 7 1381 1389 1:CAS:528:DC%2BB38XhsFCrsrbL 10.1038/s41591-022-01866-4 35715566 9205281 Epub 20220617. PubMed PMID: 35715566; PubMed Central PMCID: PMCPMC9205281
K.A. Strauss M.A. Farrar F. Muntoni K. Saito J.R. Mendell L. Servais et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial Nat Med 2022 28 7 1390 1397 1:CAS:528:DC%2BB38XhsFCrsrbE 10.1038/s41591-022-01867-3 35715567 9205287 Epub 20220617. PubMed PMID: 35715567; PubMed Central PMCID: PMCPMC9205287
R F, M F, L S, D V, E Z, M A-M, et al. RAINBOWFISH: Primary efficacy and safety data in risdiplam-treated infants with presymptomatic spinal muscular atrophy (SMA). Neuromuscul Disord. 2023;33(Sup 1):S87–S8.
D.C. De Vivo E. Bertini K.J. Swoboda W.L. Hwu T.O. Crawford R.S. Finkel et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the Phase 2 NURTURE study Neuromuscul Disord 2019 29 11 842 856 10.1016/j.nmd.2019.09.007 31704158 7127286 Epub 20190912. PubMed PMID: 31704158; PubMed Central PMCID: PMCPMC7127286
R.S. Finkel J.W. Day S.I. Pascual Pascual M.M. Ryan E. Mercuri D.C. De Vivo et al. DEVOTE study exploring higher dose of nusinersen in spinal muscular atrophy: study design and part A results J Neuromuscul Dis. 2023 10 5 813 823 10.3233/JND-221667.PubMedPMID:37393513;PubMedCentralPMCID:PMCPMC10578235 37393513 10578235
R.S. Finkel M.M. Ryan S.I. Pascual Pascual J.W. Day E. Mercuri D.C. De Vivo et al. Scientific rationale for a higher dose of nusinersen Ann Clin Transl Neurol 2022 9 6 819 829 10.1002/acn3.51562 35567345 9186144 Epub 20220513. PubMed PMID: 35567345; PubMed Central PMCID: PMCPMC9186144
F. Boemer J.H. Caberg P. Beckers V. Dideberg S. di Fiore V. Bours et al. Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium Sci Rep 2021 11 1 19922 1:CAS:528:DC%2BB3MXit1SqurbM 10.1038/s41598-021-99496-2 34620959 8497564 Epub 20211007. PubMed PMID: 34620959; PubMed Central PMCID: PMCPMC8497564
K.S. Kucera J.L. Taylor V.R. Robles K. Clinard B. Migliore B.L. Boyea et al. A voluntary statewide newborn screening pilot for spinal muscular atrophy: results from early check Int J Neonatal Screen. 2021 10.3390/ijns7010020 33801060 8006221 Epub 20210321. PubMed PMID: 33801060; PubMed Central PMCID: PMCPMC8006221
K. Vill O. Schwartz A. Blaschek D. Gläser U. Nennstiel B. Wirth et al. Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years Orphanet J Rare Dis 2021 16 1 153 10.1186/s13023-021-01783-8 33789695 8011100 Epub 20210331. PubMed PMID: 33789695; PubMed Central PMCID: PMCPMC8011100
A. Blaschek H. Kölbel O. Schwartz C. Köhler D. Gläser K. Eggermann et al. Newborn screening for SMA—can a wait-and-see strategy be responsibly justified in patients with four SMN2 copies? J Neuromuscul Dis. 2022 9 5 597 605 10.3233/JND-221510 35848034 PubMed PMID: 35848034
S. Sonehara R. Bo Y. Nambu K. Iketani T. Lee H. Shimomura et al. Newborn screening for spinal muscular atrophy: a 25-year experience in Hyogo Prefecture, Japan Genes (Basel) 2023 10.3390/genes14122211 38137033 10081410 Epub 20231214. PubMed PMID: 38137033; PubMed Central PMCID: PMCPMC10742789
B.H. Lee S. Deng C.A. Chiriboga D.M. Kay O. Irumudomon E. Laureta et al. Newborn screening for spinal muscular atrophy in new york state: clinical outcomes from the first 3 years Neurology 2022 99 14 e1527 e1537 10.1212/WNL.0000000000200986 35835557 9576300 Epub 20221003. PubMed PMID: 35835557; PubMed Central PMCID: PMCPMC9576300
J. Matteson C.H. Wu D. Mathur H. Tang S. Sciortino L. Feuchtbaum et al. California's experience with SMA newborn screening: a successful path to early intervention J Neuromuscul Dis. 2022 9 6 777 785 10.3233/JND-221561 36278357 PubMed PMID: 36278357
K. Elkins A. Wittenauer A.F. Hagar R. Logan E. Sekul Y. Xiang et al. Georgia state spinal muscular atrophy newborn screening experience: screening assay performance and early clinical outcomes Am J Med Genet C Semin Med Genet 2022 190 2 187 196 10.1002/ajmg.c.32003 36164257 Epub 20220926. PubMed PMID: 36164257
D.S. Kariyawasam A.M. D'Silva H. Sampaio N. Briggs K. Herbert V. Wiley et al. Newborn screening for spinal muscular atrophy in Australia: a non-randomised cohort study Lancet Child Adolesc Health. 2023 7 3 159 170 10.1016/S2352-4642(22)00342-X 36669516 Epub 20230117. PubMed PMID: 36669516
O. Schwartz H. Kölbel A. Blaschek D. Gläser S. Burggraf W. Röschinger et al. Spinal muscular atrophy—is newborn screening too late for children with two SMN2 copies? J Neuromuscul Dis. 2022 9 3 389 396 10.3233/JND-220789 35431259 PubMed PMID: 35431259
H. Kölbel M. Kopka L. Modler A. Blaschek U. Schara-Schmidt K. Vill et al. Impaired neurodevelopment in children with 5q-SMA—2 years after newborn screening J Neuromuscul Dis. 2024 11 1 143 151 10.3233/JND-230136 37927272 10789341 PubMed PMID: 37927272
B. Buchignani G. Cicala F. Cumbo M. Ricci A. Capasso C. Ticci et al. Communicative development inventory in type 1 and presymptomatic infants with spinal muscular atrophy: a cohort study Arch Dis Child 2024 10.1136/archdischild-2023-326613 38290776 Epub 20240130. PubMed PMID: 38290776
Y. Erbas N. Gusset The need for evidence-based treatment decisions in spinal muscular atrophy type 0 Ann Clin Transl Neurol 2021 8 10 2094 2095 10.1002/acn3.51459 34546649 8528450 Epub 20210921. PubMed PMID: 34546649; PubMed Central PMCID: PMCPMC8528450
E. Tiberi S. Costa M. Pane F. Priolo R. de Sanctis D. Romeo et al. Nusinersen in type 0 spinal muscular atrophy: should we treat? Ann Clin Transl Neurol 2020 7 12 2481 2483 1:CAS:528:DC%2BB3MXhtFyku7k%3D 10.1002/acn3.51126 33147378 7732235 Epub 20201104. PubMed PMID: 33147378; PubMed Central PMCID: PMCPMC7732235
R.H. Mendonça A.J. Rocha A. Lozano-Arango A.B. Diaz C. Castiglioni A.M.S. Silva et al. Severe brain involvement in 5q spinal muscular atrophy type 0 Ann Neurol 2019 86 3 458 462 1:CAS:528:DC%2BC1MXhsF2rsLrO 10.1002/ana.25549 31301241 Epub 20190724. PubMed PMID: 31301241
M. Tosi F. Cumbo M. Catteruccia A. Carlesi I. Mizzoni G. De Luca et al. Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers Eur J Paediatr Neurol 2023 43 36 43 1:CAS:528:DC%2BB3sXlsVaqs7o%3D 10.1016/j.ejpn.2023.02.004 36893678 Epub 20230303. PubMed PMID: 36893678
R.S. Finkel C.A. Chiriboga J. Vajsar J.W. Day J. Montes D.C. De Vivo et al. 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. 2021 5 7 491 500 1:CAS:528:DC%2BB3MXhvVCrtr7E 10.1016/S2352-4642(21)00100-0 34089650
R.S. Finkel E. Mercuri B.T. Darras A.M. Connolly N.L. Kuntz J. Kirschner et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy N Engl J Med 2017 377 18 1723 1732 1:CAS:528:DC%2BC2sXhvFChtbfF 10.1056/NEJMoa1702752 29091570 PubMed PMID: 29091570
L. Servais M. Farrar R. Finkel J. Kirschner F. Muntoni P. Sun et al. Nusinersen demonstrates greater efficacy in infants with shorter disease duration: end of study results from the ENDEAR study in infants with spinal muscular atrophy (SMA) Neuromuscul Disord 2017 27 S211 10.1016/j.nmd.2017.06.421
J.R. Mendell S. Al-Zaidy R. Shell W.D. Arnold L.R. Rodino-Klapac T.W. Prior et al. Single-dose gene-replacement therapy for spinal muscular atrophy N Engl J Med 2017 377 18 1713 1722 1:CAS:528:DC%2BC2sXhvFChur7K 10.1056/NEJMoa1706198 29091557 PubMed PMID: 29091557
J.R. Mendell S.A. Al-Zaidy K.J. Lehman M. McColly L.P. Lowes L.N. Alfano et al. Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy JAMA Neurol 2021 78 7 834 841 10.1001/jamaneurol.2021.1272 33999158 PubMed PMID: 33999158; PubMed Central PMCID: PMCPMC8129901
E. Mercuri F. Muntoni G. Baranello R. Masson O. Boespflug-Tanguy C. Bruno et al. 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 2021 20 10 832 841 1:CAS:528:DC%2BB3MXisVClsbnJ 10.1016/S1474-4422(21)00251-9 34536405 PubMed PMID: 34536405
S. Al-Zaidy A.S. Pickard K. Kotha L.N. Alfano L. Lowes G. Paul et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy Pediatr Pulmonol 2019 54 2 179 185 10.1002/ppul.24203 30548438
R. Masson M. Mazurkiewicz-Bełdzińska K. Rose L. Servais H. Xiong E. Zanoteli et al. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial Lancet Neurol 2022 21 12 1110 1119 1:CAS:528:DC%2BB38Xis1yqtrjL 10.1016/S1474-4422(22)00339-8 36244364 Epub 20221014. PubMed PMID: 36244364
Chan SH-S, Chae J-H, Chien Y-H, Ko T-S, Lee JH, Lee YJ, et al. Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions. J Neurol Neurosurg Psychiatry. 2021.
S. Modrzejewska K. Kotulska I. Kopyta E. Grędowska E. Emich-Widera K. Tomaszek et al. Nusinersen treatment of Spinal Muscular Atrophy Type 1—results of expanded access programme in Poland Neurol Neurochir Pol 2021 55 3 289 294 10.5603/PJNNS.a2021.0020 33565602 Epub 20210210. PubMed PMID: 33565602
de Holanda Mendonça R, Jorge Polido G, Ciro Jr M, Jorge Fontoura Solla D, Conti Reed U, Zanoteli E. Clinical outcomes in patients with spinal muscular atrophy type 1 treated with nusinersen. J Neuromuscul Dis. 2021;8(2):217–24.
F. Audic M.G.G. de La Banda D. Bernoux P. Ramirez-Garcia J. Durigneux C. Barnerias et al. 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 2020 15 1 1 10 10.1186/s13023-020-01414-8
A. Łusakowska A. Wójcik A. Frączek K. Aragon-Gawińska A. Potulska-Chromik P. Baranowski et al. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience Orphanet J Rare Dis 2023 18 1 230 10.1186/s13023-023-02769-4 37542300 10401775 Epub 20230804. PubMed PMID: 37542300; PubMed Central PMCID: PMCPMC10401775
V.A. Sansone A. Pirola E. Albamonte M. Pane A. Lizio A. D'Amico et al. Respiratory needs in patients with type 1 spinal muscular atrophy treated with nusinersen J Pediatr 2020 219 223 8.e4 10.1016/j.jpeds.2019.12.047 32035635 Epub 20200205. PubMed PMID: 32035635
M. Lavie N. Diamant M. Cahal E. Sadot M. Be'er A. Fattal-Valevski et al. Nusinersen for spinal muscular atrophy type 1: Real-world respiratory experience Pediatr Pulmonol 2021 56 1 291 298 10.1002/ppul.25140 33111497 Epub 20201105. PubMed PMID: 33111497
F. Al Amrani R. Amin J. Chiang L. Xiao J. Boyd E. Law et al. Scoliosis in spinal muscular atrophy type 1 in the nusinersen era Neurol Clin Pract 2022 12 4 279 287 10.1212/CPJ.0000000000001179 36382115 9647826
A. Chacko P.D. Sly R.S. Ware N. Begum S. Deegan N. Thomas et al. Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1–3 Thorax 2022 77 1 40 46 10.1136/thoraxjnl-2020-216564 33963091 Epub 20210507. PubMed PMID: 33963091
K. Aragon-Gawinska A.M. Seferian A. Daron E. Gargaun C. Vuillerot C. Cances et al. Nusinersen in patients older than 7 months with spinal muscular atrophy type 1: a cohort study Neurology 2018 91 14 e1312 e1318 1:CAS:528:DC%2BC1cXhvVWisLbF 10.1212/WNL.0000000000006281 30158155
M. Pane G. Coratti V.A. Sansone S. Messina C. Bruno M. Catteruccia et al. Nusinersen in type 1 spinal muscular atrophy: twelve-month real-world data Ann Neurol 2019 86 3 443 451 1:CAS:528:DC%2BC1MXhsF2rsLrK 10.1002/ana.25533 31228281
H. Weststrate G. Stimpson L. Thomas M. Scoto E. Johnson A. Stewart et al. Evolution of bulbar function in spinal muscular atrophy type 1 treated with nusinersen Dev Med Child Neurol 2022 64 7 907 914 10.1111/dmcn.15171 35103306 9306995
A.M. D'Silva S. Holland D. Kariyawasam K. Herbert P. Barclay A. Cairns et al. Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy Ann Clin Transl Neurol 2022 9 3 339 350 10.1002/acn3.51519 35170254 8935277 Epub 20220216. PubMed PMID: 35170254; PubMed Central PMCID: PMCPMC8935277
S. Lee Y.J. Lee J. Kong H.W. Ryu Y.K. Shim J.Y. Han et al. Short-term clinical outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy Brain Dev 2022 44 4 287 293 1:CAS:528:DC%2BB38XisVCks7rM 10.1016/j.braindev.2021.12.006 35033405 Epub 20220113. PubMed PMID: 35033405
G.M. Stettner O. Hasselmann A. Tscherter E. Galiart D. Jacquier A. Klein Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study BMC Neurol 2023 23 1 88 1:CAS:528:DC%2BB3sXktFOktL8%3D 10.1186/s12883-023-03133-6 36855136 9971686 Epub 20230228. PubMed PMID: 36855136; PubMed Central PMCID: PMCPMC9971686
M.A. Waldrop S. Chagat M. Storey A. Meyer M. Iammarino N. Reash et al. Continued safety and long-term effectiveness of onasemnogene abeparvovec in Ohio Neuromuscul Disord 2024 34 41 48 10.1016/j.nmd.2023.11.010 38142474 Epub 20231202. PubMed PMID: 38142474
J.M. Kwon K. Arya N. Kuntz H.C. Phan C. Sieburg K.J. Swoboda et al. An expanded access program of risdiplam for patients with Type 1 or 2 spinal muscular atrophy Ann Clin Transl Neurol 2022 9 6 810 818 1:CAS:528:DC%2BB38XhsVaiurjJ 10.1002/acn3.51560 35567422 9186129 Epub 20220514. PubMed PMID: 35567422; PubMed Central PMCID: PMCPMC9186129
A. Hahn R. Günther A. Ludolph O. Schwartz R. Trollmann P. Weydt et al. Short-term safety results from compassionate use of risdiplam in patients with spinal muscular atrophy in Germany Orphanet J Rare Dis 2022 17 1 276 10.1186/s13023-022-02420-8 35854272 9295446
Chiriboga CA, Darras BT, Farrar MA, Mercuri E, Kirschner J, Kuntz NL, et al. Longer-term treatment with nusinersen: results in later-onset spinal muscular atrophy from the shine study (1661). AAN Enterprises; 2020.
Servais L, Oskoui M, Day J, Deconinck N, Mazzone E, Nascimento A, et al. SUNFISH Parts 1 and 2: 4-year efficacy and safety data of risdiplam in types 2 and 3 spinal muscular atrophy (SMA)(S34. 009). AAN Enterprises; 2023.
Finkel RS, Darras BT, Mendell JR, Day JW, Kuntz NL, Connolly AM, et al. Intrathecal onasemnogene abeparvovec for sitting, nonambulatory patients with spinal muscular atrophy: phase I ascending-dose study (STRONG). J Neuromuscul Dis. 2023;(Preprint):1–16.
D.M. Ramos C. d’Ydewalle V. Gabbeta A. Dakka S.K. Klein D.A. Norris et al. Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment J Clin Investig 2019 129 11 4817 4831 1:CAS:528:DC%2BB3cXnsVKjtbg%3D 10.1172/JCI124120 31589162 6819103
C.M. Proud E. Mercuri R.S. Finkel J. Kirschner D.C. De Vivo F. Muntoni et al. Combination disease-modifying treatment in spinal muscular atrophy: a proposed classification Ann Clin Transl Neurol 2023 10 11 2155 2160 1:CAS:528:DC%2BB3sXhvFemsL%2FF 10.1002/acn3.51889 37691296 10646995 Epub 20230910. PubMed PMID: 37691296; PubMed Central PMCID: PMCPMC10646995
C.A. Chiriboga C. Bruno T. Duong D. Fischer E. Mercuri J. Kirschner et al. Risdiplam in patients previously treated with other therapies for spinal muscular atrophy: an interim analysis from the JEWELFISH Study Neurol Ther. 2023 12 2 543 557 10.1007/s40120-023-00444-1 36780114 9924181 Epub 20230213. PubMed PMID: 36780114; PubMed Central PMCID: PMCPMC9924181
A. Mirea E.S. Shelby M. Axente M. Badina L. Padure M. Leanca et al. Combination therapy with nusinersen and onasemnogene abeparvovec-xioi in spinal muscular atrophy type I J Clin Med 2021 10.3390/jcm10235540 34884240 8658131 Epub 20211126. PubMed PMID: 34884240; PubMed Central PMCID: PMCPMC8658131
Y. Harada V.K. Rao K. Arya N.L. Kuntz C.J. DiDonato G. Napchan-Pomerantz et al. Combination molecular therapies for type 1 spinal muscular atrophy Muscle Nerve 2020 62 4 550 554 1:CAS:528:DC%2BB3cXhvV2ktr3J 10.1002/mus.27034 32710634 Epub 20200810. PubMed PMID: 32710634
F. Rouault V. Christie-Brown R. Broekgaarden N. Gusset D. Henderson P. Marczuk et al. Disease impact on general well-being and therapeutic expectations of European Type II and Type III spinal muscular atrophy patients Neuromuscul Disord 2017 27 5 428 438 10.1016/j.nmd.2017.01.018 28237437
N. Gusset C. Stalens E. Stumpe L. Klouvi A. Mejat M.C. Ouillade et al. Understanding European patient expectations towards current therapeutic development in spinal muscular atrophy Neuromuscul Disord 2021 31 5 419 430 10.1016/j.nmd.2021.01.012 33752935 Epub 20210204. PubMed PMID: 33752935
A. Monnette E. Chen D. Hong A. Bazzano S. Dixon W.D. Arnold et al. Treatment preference among patients with spinal muscular atrophy (SMA): a discrete choice experiment Orphanet J Rare Dis 2021 16 1 36 10.1186/s13023-020-01667-3 33472673 7819167 Epub 20210120. PubMed PMID: 33472673; PubMed Central PMCID: PMCPMC7819167
T. Dangouloff C. Botty C. Beaudart L. Servais M. Hiligsmann Systematic literature review of the economic burden of spinal muscular atrophy and economic evaluations of treatments Orphanet J Rare Dis 2021 16 1 47 10.1186/s13023-021-01695-7 33485382 7824917 Epub 20210123. PubMed PMID: 33485382; PubMed Central PMCID: PMCPMC7824917
T. Dangouloff P. Thokala M.D. Stevenson N. Deconinck A. D'Amico A. Daron et al. Cost-effectiveness of spinal muscular atrophy newborn screening based on real-world data in Belgium Neuromuscul Disord 2023 34 61 67 10.1016/j.nmd.2023.11.013 38150893 Epub 20231202. PubMed PMID: 38150893
D. Weidlich L. Servais I. Kausar R. Howells M. Bischof Cost-effectiveness of newborn screening for spinal muscular atrophy in England Neurol Ther. 2023 12 4 1205 1220 10.1007/s40120-023-00489-2 37222861 10310612 Epub 20230524. PubMed PMID: 37222861; PubMed Central PMCID: PMCPMC10310612
L. Servais G. Baranello M. Scoto A. Daron M. Oskoui Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities Expert Opin Investig Drugs 2021 30 5 519 527 1:CAS:528:DC%2BB3MXos1CgtL8%3D 10.1080/13543784.2021.1904889 33749510 Epub 20210413. PubMed PMID: 33749510
V. Mariot R. Joubert C. Hourdé L. Féasson M. Hanna F. Muntoni et al. Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches Nat Commun 2017 8 1 1859 1:CAS:528:DC%2BC1cXptFSgsbo%3D 10.1038/s41467-017-01486-4 29192144 5709430 Epub 20171130. PubMed PMID: 29192144; PubMed Central PMCID: PMCPMC5709430
M. Stam C.A. Wijngaarde B. Bartels F.L. Asselman L.A.M. Otto L.E. Habets et al. Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2–4 Brain Commun. 2023 5 1 fcac324 1:CAS:528:DC%2BB3sXpsFWrsLo%3D 10.1093/braincomms/fcac324 36632180 Epub 20221209. PubMed PMID: 36632180; PubMed Central PMCID: PMCPMC9825780
T. Dangouloff L. Servais Clinical evidence supporting early treatment of patients with spinal muscular atrophy: current perspectives Ther Clin Risk Manag 2019 15 1153 1161 1:CAS:528:DC%2BB3cXmvFerurk%3D 10.2147/TCRM.S172291 31632042 6778729 Epub 20191002. PubMed PMID: 31632042; PubMed Central PMCID: PMCPMC6778729
S.T.F. Shih E. Keller V. Wiley M.A. Farrar M. Wong G.M. Chambers Modelling the cost-effectiveness and budget impact of a newborn screening program for spinal muscular atrophy and severe combined immunodeficiency Int J Neonatal Screen. 2022 10.3390/ijns8030045 35892475 9326684 Epub 20220720. PubMed PMID: 35892475; PubMed Central PMCID: PMCPMC9326684
R. Velikanova S. van der Schans M. Bischof R.W. van Olden M. Postma C. Boersma Cost-effectiveness of newborn screening for spinal muscular atrophy in The Netherlands Value Health. 2022 25 10 1696 1704 10.1016/j.jval.2022.06.010 35963838 Epub 20220811. PubMed PMID: 35963838
C. Agosto F. Benedetti E. Salamon A. Mercante S. Papa L. Giacomelli et al. How children and caregivers viewed the change from nusinersen to risdiplam for treating spinal muscular atrophy Acta Paediatr 2023 112 2 311 312 10.1111/apa.16568 36222023 Epub 20221018. PubMed PMID: 36222023
J.C. Powell J.B. Meiling M.S. Cartwright A case series evaluating patient perceptions after switching from nusinersen to risdiplam for spinal muscular atrophy Muscle Nerve 2024 69 2 179 184 10.1002/mus.28015 38040488 Epub 20231201. PubMed PMID: 38040488
