{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:00:22Z","timestamp":1785218422732,"version":"3.55.0"},"reference-count":150,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disorder characterized by progressive degeneration of lower motor neurons, leading to muscle weakness and atrophy predominantly manifesting in childhood. The disease is caused by homozygous deletion or loss-of-function mutations in the survival motor neuron 1 (SMN1) gene, with the nearly identical SMN2 gene acting as a critical modifier of disease severity. Since the initial clinical descriptions in 1891 and the identification of the causative gene in 1995, the field has witnessed transformative therapeutic progress. The FDA approval of nusinersen, an antisense oligonucleotide targeting SMN2 splicing, in 2016 marked the first disease-modifying therapy, followed by the gene replacement therapy onasemnogene abeparvovec in 2019 and the orally administered small-molecule splicing modifier risdiplam in 2020. These SMN-targeted therapies have substantially improved survival and motor outcomes, particularly when administered presymptomatically as enabled by increasingly widespread newborn screening programs. However, a significant proportion of patients, especially those with later-onset disease and adults, show limited responses, and existing therapies cannot reverse established neurodegeneration or muscle pathology. In this review, we trace the history of SMA research and therapy development, critically compare the three approved treatments, and discuss key unresolved challenges including treatment-switching criteria, management of late-diagnosed patients, and the emerging role of biomarkers such as neurofilament light chain and compound muscle action potential. We further explore non-SMN therapeutic strategies targeting PTEN, plastin 3, neurocalcin delta, myostatin, and neuroinflammation, and examine the rationale for combination approaches that integrate SMN restoration with muscle- and neuro-protective agents. Finally, we address future directions encompassing precision medicine, next-generation gene editing, and biomarker-driven trial design. While SMA has been transformed from a fatal childhood disorder to a treatable condition, a definitive cure for all patients remains the goal of ongoing and future research.<\/jats:p>","DOI":"10.3389\/fnhum.2026.1833269","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:32Z","timestamp":1785217052000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic strategies for spinal muscular atrophy: the history and future perspective"],"prefix":"10.3389","volume":"20","author":[{"given":"Jiayi","family":"Liu","sequence":"first","affiliation":[{"name":"Jinfeng Laboratory","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Chengdu Women\u2019s and Children\u2019s Center Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Jinfeng Laboratory","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ning","sequence":"additional","affiliation":[{"name":"Jinfeng Laboratory","place":["Chongqing, China"]},{"name":"Sheffield Institute of Translational Neuroscience (SITraN), University of Sheffield","place":["Sheffield, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/hmg\/dds540","article-title":"Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality","volume":"22","author":"Ackermann","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/apa.16568","article-title":"How children and caregivers viewed the change from nusinersen to risdiplam for treating spinal muscular atrophy","volume":"112","author":"Agosto","year":"2023","journal-title":"Acta Paediatr."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s13023-020-01593-4","article-title":"Do we always need to treat patients with spinal muscular atrophy? A personal view and experience","volume":"16","author":"Agosto","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"32","DOI":"10.4103\/2231-0770.197512","article-title":"Very severe spinal muscular atrophy (type 0)","volume":"7","author":"Al Dakhoul","year":"2017","journal-title":"Avicenna J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/febs.14608","article-title":"Endoplasmic reticulum stress signalling \u2013 from basic mechanisms to clinical applications","volume":"286","author":"Almanza","year":"2019","journal-title":"FEBS J."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00415-025-13557-4","article-title":"Safety and effectiveness of risdiplam in adults with spinal muscular atrophy: a systematic review","volume":"273","author":"Alonge","year":"2025","journal-title":"J. Neurol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/sj.ejhg.5201102","article-title":"Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy","volume":"12","author":"Andreassi","year":"2004","journal-title":"Eur. J. Hum. Genet."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.3390\/ijms25073810","article-title":"Neurodegeneration biomarkers in adult spinal muscular atrophy (SMA) patients treated with Nusinersen","volume":"25","author":"Andr\u00e9s-Benito","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/mus.24497","article-title":"Spinal muscular atrophy: diagnosis and management in a new therapeutic era","volume":"51","author":"Arnold","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.arcped.2023.10.009","article-title":"Effect of nusinersen after 3 years of treatment in 57 young children with SMA in terms of SMN2 copy number or type","volume":"31","author":"Audic","year":"2024","journal-title":"Arch. Pediatr."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1172\/jci22922","article-title":"Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy","volume":"114","author":"Azzouz","year":"2004","journal-title":"J. Clin. Invest."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.1007\/s12325-021-01757-z","article-title":"A randomized phase 1 safety, pharmacokinetic and pharmacodynamic study of the novel myostatin inhibitor Apitegromab (SRK-015): a potential treatment for spinal muscular atrophy","volume":"38","author":"Barrett","year":"2021","journal-title":"Adv. Ther."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3390\/neurolint17030041","article-title":"Glial cells in spinal muscular atrophy: speculations on non-cell-autonomous mechanisms and therapeutic implications","volume":"17","author":"Belan\u010di\u0107","year":"2025","journal-title":"Neurol. Int."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1093\/hmg\/ddq300","article-title":"Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery","volume":"19","author":"Bevan","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3233\/jnd-221510","article-title":"Newborn screening for SMA \u2013 can a wait-and-see strategy be responsibly justified in patients with four SMN2 copies?","volume":"9","author":"Blaschek","year":"2022","journal-title":"J Neuromuscul Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1111\/bpa.12071","article-title":"Spinal muscular atrophy: new findings for an old pathology","volume":"23","author":"Bottai","year":"2013","journal-title":"Brain Pathol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1093\/hmg\/ddq021","article-title":"Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model","volume":"19","author":"Bowerman","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1242\/dmm.030148","article-title":"Therapeutic strategies for spinal muscular atrophy: SMN and beyond","volume":"10","author":"Bowerman","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e1006744","DOI":"10.1371\/journal.pgen.1006744","article-title":"Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy","volume":"13","author":"Boyd","year":"2017","journal-title":"PLoS Genet."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.1093\/hmg\/ddg256","article-title":"Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy","volume":"12","author":"Brichta","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/344540a0","article-title":"Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3","volume":"344","author":"Brzustowicz","year":"1990","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/nrn2670","article-title":"Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?","volume":"10","author":"Burghes","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1006\/geno.1996.0147","article-title":"Structure and organization of the human survival motor neurone (SMN) gene","volume":"32","author":"B\u00fcrglen","year":"1996","journal-title":"Genomics"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1128\/mcb.01262-08","article-title":"Regulation of SMN protein stability","volume":"29","author":"Burnett","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1086\/498853","article-title":"Determinants of exon 7 splicing in the spinal muscular atrophy genes, SMN1 and SMN2","volume":"78","author":"Cartegni","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/nsb887","article-title":"Correction of disease-associated exon skipping by synthetic exon-specific activators","volume":"10","author":"Cartegni","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1083\/jcb.147.4.715","article-title":"The spinal muscular atrophy disease gene product, SMN: a link between snRNP biogenesis and the Cajal (coiled) body","volume":"147","author":"Carvalho","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1083\/jcb.148.6.1177","article-title":"Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli","volume":"148","author":"Charroux","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"100346","DOI":"10.1016\/j.xcrm.2021.100346","article-title":"Spinal muscular atrophy: from approved therapies to future therapeutic targets for personalized medicine","volume":"2","author":"Chaytow","year":"2021","journal-title":"Cell Rep Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1007\/s00018-018-2849-1","article-title":"The role of survival motor neuron protein (SMN) in protein homeostasis","volume":"75","author":"Chaytow","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1101\/gad.1884910","article-title":"A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity","volume":"24","author":"Cho","year":"2010","journal-title":"Genes Dev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","article-title":"The survival motor neuron protein in spinal muscular atrophy","volume":"6","author":"Coovert","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/s1474-4422(25)00225-x","article-title":"Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial","volume":"24","author":"Crawford","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.nmd.2019.11.002","article-title":"244th ENMC international workshop: newborn screening in spinal muscular atrophy may 10-12, 2019, Hoofdorp, the Netherlands","volume":"30","author":"Dangouloff","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.nmd.2021.03.007","article-title":"Newborn screening programs for spinal muscular atrophy worldwide: where we stand and where to go","volume":"31","author":"Dangouloff","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1186\/s12887-022-03671-x","article-title":"Advances and limitations for the treatment of spinal muscular atrophy","volume":"22","author":"Day","year":"2022","journal-title":"BMC Pediatr."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","article-title":"Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study","volume":"29","author":"De Vivo","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.retram.2016.04.001","article-title":"Human induced pluripotent stem cells: a disruptive innovation","volume":"64","author":"De Vos","year":"2016","journal-title":"Curr Res Transl Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1093\/nar\/gkw731","article-title":"RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns","volume":"45","author":"Doktor","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.conb.2016.04.004","article-title":"A role for the survival of motor neuron protein in mRNP assembly and transport","volume":"39","author":"Donlin-Asp","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature07677","article-title":"Induced pluripotent stem cells from a spinal muscular atrophy patient","volume":"457","author":"Ebert","year":"2009","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1750-1326-5-17","article-title":"High-efficiency transfection of cultured primary motor neurons to study protein localization, trafficking, and function","volume":"5","author":"Fallini","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.brainres.2012.01.044","article-title":"Spinal muscular atrophy: the role of SMN in axonal mRNA regulation","volume":"1462","author":"Fallini","year":"2012","journal-title":"Brain Res."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1093\/hmg\/11.14.1605","article-title":"Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development","volume":"11","author":"Fan","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref45","doi-asserted-by":"publisher","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":"Feldk\u00f6tter","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref46","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":"ref47","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/s0092-8674(00)80368-2","article-title":"The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis","volume":"90","author":"Fischer","year":"1997","journal-title":"Cell"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nbt.1515","article-title":"Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes","volume":"27","author":"Foust","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/345823a0","article-title":"Genetic homogeneity between acute and chronic forms of spinal muscular atrophy","volume":"345","author":"Gilliam","year":"1990","journal-title":"Nature"},{"key":"ref50","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":"ref51","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1007\/s12035-017-0831-9","article-title":"Time is motor neuron: therapeutic window and its correlation with pathogenetic mechanisms in spinal muscular atrophy","volume":"55","author":"Govoni","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"100817","DOI":"10.1016\/j.lanepe.2023.100817","article-title":"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","volume":"37","author":"Gowda","year":"2024","journal-title":"The Lancet Regional Health \u2013 Europe"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.molmed.2015.08.003","article-title":"UBA1: at the crossroads of ubiquitin homeostasis and neurodegeneration","volume":"21","author":"Groen","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/s1474-4422(18)30320-x","article-title":"Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial","volume":"17","author":"Grunseich","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s00415-002-0811-4","article-title":"Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity","volume":"249","author":"Harada","year":"2002","journal-title":"J. Neurol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"5ra12","DOI":"10.1126\/scitranslmed.3000208","article-title":"Tetracyclines that promote SMN2 exon 7 splicing as therapeutics for spinal muscular atrophy","volume":"1","author":"Hastings","year":"2009","journal-title":"Sci. Transl. Med."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"6191","DOI":"10.1038\/s41467-024-50095-5","article-title":"Therapeutic strategy for spinal muscular atrophy by combining gene supplementation and genome editing","volume":"15","author":"Hatanaka","year":"2024","journal-title":"Nat. Commun."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1093\/hmg\/ddn357","article-title":"Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition","volume":"18","author":"Hauke","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"2720","DOI":"10.1101\/gad.908401","article-title":"Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein","volume":"15","author":"Hebert","year":"2001","journal-title":"Genes Dev."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1177\/1073858417705059","article-title":"The actin cytoskeleton in SMA and ALS: how does it contribute to motoneuron degeneration?","volume":"24","author":"Hensel","year":"2018","journal-title":"Neuroscientist"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.ajhg.2016.07.014","article-title":"The power of human protective modifiers: PLS3 and CORO1C unravel impaired endocytosis in spinal muscular atrophy and rescue SMA phenotype","volume":"99","author":"Hosseinibarkooie","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/71709","article-title":"A mouse model for spinal muscular atrophy","volume":"24","author":"Hsieh-Li","year":"2000","journal-title":"Nat. Genet."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature10485","article-title":"Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model","volume":"478","author":"Hua","year":"2011","journal-title":"Nature"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.ajhg.2008.01.014","article-title":"Antisense masking of an hnRNP A1\/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice","volume":"82","author":"Hua","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref65","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/B978-0-12-803685-3.00026-4","volume-title":"Spinal Muscular Atrophy","author":"Iannaccone","year":"2017"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"e202201457","DOI":"10.26508\/lsa.202201457","article-title":"SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axis","volume":"6","author":"Ikenaka","year":"2023","journal-title":"Life Sci Alliance"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1093\/hmg\/ddn156","article-title":"Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy","volume":"17","author":"Kariya","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"100742","DOI":"10.1016\/j.eclinm.2021.100742","article-title":"\"we needed this\": perspectives of parents and healthcare professionals involved in a pilot newborn screening program for spinal muscular atrophy","volume":"33","author":"Kariyawasam","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/ng1207","article-title":"A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy","volume":"34","author":"Kashima","year":"2003","journal-title":"Nat. Genet."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/s41467-022-28653-6","article-title":"An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion","volume":"13","author":"Keller","year":"2022","journal-title":"Nat. Commun."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1093\/hmg\/ddi130","article-title":"The role of histone acetylation in SMN gene expression","volume":"14","author":"Kernochan","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1172\/jci131989","article-title":"Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models","volume":"130","author":"Kim","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"e21296","DOI":"10.1371\/journal.pone.0021296","article-title":"SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy","volume":"6","author":"Kissel","year":"2011","journal-title":"PLoS One"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1007\/s12325-024-02845-6","article-title":"Long-term comparative efficacy and safety of Risdiplam and Nusinersen in children with type 1 spinal muscular atrophy","volume":"41","author":"Kokaliaris","year":"2024","journal-title":"Adv. Ther."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1523\/jneurosci.4434-08.2009","article-title":"Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice","volume":"29","author":"Kong","year":"2009","journal-title":"J. Neurosci."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"694","DOI":"10.3390\/children8080694","article-title":"Views of the general population on newborn screening for spinal muscular atrophy in Japan","volume":"8","author":"Lee","year":"2021","journal-title":"Children (Basel)"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/ng0797-265","article-title":"Correlation between severity and SMN protein level in spinal muscular atrophy","volume":"16","author":"Lefebvre","year":"1997","journal-title":"Nat. Genet."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.3390\/neurolint16060096","article-title":"Efficacy of Nusinersen treatment in type 1, 2, and 3 spinal muscular atrophy: real-world data from a single-Center study","volume":"16","author":"Lemska","year":"2024","journal-title":"Neurol. Int."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/jcb.10312","article-title":"PTEN regulation of neural development and CNS stem cells","volume":"88","author":"Li","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s13023-025-03857-3","article-title":"Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions","volume":"20","author":"Li","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"4160","DOI":"10.1038\/srep04160","article-title":"A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources","volume":"4","author":"Lippmann","year":"2014","journal-title":"Sci. Rep."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1002\/j.1460-2075.1996.tb00725.x","article-title":"A novel nuclear structure containing the survival of motor neurons protein","volume":"15","author":"Liu","year":"1996","journal-title":"EMBO J."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/s0092-8674(00)80367-0","article-title":"The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins","volume":"90","author":"Liu","year":"1997","journal-title":"Cell"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/ng0598-63","article-title":"SMN oligomerization defect correlates with spinal muscular atrophy severity","volume":"19","author":"Lorson","year":"1998","journal-title":"Nat. Genet."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0959-4388(97)80124-9","article-title":"Rho family small GTP-binding proteins in growth cone signalling","volume":"7","author":"Luo","year":"1997","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/00125817-200201000-00004","article-title":"Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2","volume":"4","author":"Mailman","year":"2002","journal-title":"Genet. Med."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1016\/j.str.2012.08.024","article-title":"The survival motor neuron protein forms soluble glycine zipper oligomers","volume":"20","author":"Martin","year":"2012","journal-title":"Structure"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1086\/515465","article-title":"Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number","volume":"60","author":"McAndrew","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/344767a0","article-title":"Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q","volume":"344","author":"Melki","year":"","journal-title":"Nature"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0140-6736(90)91803-i","article-title":"Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14. The French spinal muscular atrophy investigators","volume":"336","author":"Melki","year":"","journal-title":"Lancet"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1001\/jamaneurol.2021.1272","article-title":"Five-year extension results of the phase 1 START trial of Onasemnogene Abeparvovec in spinal muscular atrophy","volume":"78","author":"Mendell","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref94","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":"ref95","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus sham control in later-onset spinal muscular atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"e2300308120","DOI":"10.1073\/pnas.2300308120","article-title":"Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy","volume":"120","author":"Miller","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1093\/hmg\/9.3.333","article-title":"The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in SMN(\u2212\/\u2212) mice and results in a mouse with spinal muscular atrophy","volume":"9","author":"Monani","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.neuron.2005.12.001","article-title":"Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease","volume":"48","author":"Monani","year":"2005","journal-title":"Neuron"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"e413","DOI":"10.1212\/wnl.0000000000009914","article-title":"Nusinersen in adult patients with spinal muscular atrophy: observations from a single center","volume":"95","author":"Moshe-Lilie","year":"2020","journal-title":"Neurology"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3233\/jnd-200475","article-title":"Infants diagnosed with spinal muscular atrophy and 4 SMN2 copies through newborn screening \u2013 opportunity or burden?","volume":"7","author":"M\u00fcller-Felber","year":"2020","journal-title":"J Neuromuscul Dis"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"4334","DOI":"10.1093\/hmg\/ddr360","article-title":"Reversible molecular pathology of skeletal muscle in spinal muscular atrophy","volume":"20","author":"Mutsaers","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"101921","DOI":"10.1016\/j.molmet.2024.101921","article-title":"Salubrinal promotes phospho-eIF2\u03b1-dependent activation of UPR leading to autophagy-mediated attenuation of iron-induced insulin resistance","volume":"83","author":"Nguyen","year":"2024","journal-title":"Mol Metab"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1093\/hmg\/ddq226","article-title":"PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons","volume":"19","author":"Ning","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"11939","DOI":"10.3390\/ijms241511939","article-title":"Spinal muscular atrophy: the past, present, and future of diagnosis and treatment","volume":"24","author":"Nishio","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.3390\/genes13112110","article-title":"PCR-based screening of spinal muscular atrophy for newborn infants in Hyogo prefecture, Japan","volume":"13","author":"Noguchi","year":"2022","journal-title":"Genes (Basel)"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s43856-023-00256-2","article-title":"Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients","volume":"3","author":"Nuzzo","year":"2023","journal-title":"Commun. Med. (Lond.)"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/ijns8040052","article-title":"Changes in the incidence of infantile spinal muscular atrophy in Shikoku, Japan between 2011 and 2020","volume":"8","author":"Okamoto","year":"2022","journal-title":"Int. J. Neonatal Screen."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1126\/science.1155085","article-title":"Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy","volume":"320","author":"Oprea","year":"2008","journal-title":"Science"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nchembio.1837","article-title":"SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice","volume":"11","author":"Palacino","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/phar.2866","article-title":"Efficacy of risdiplam in spinal muscular atrophy: a systematic review and meta-analysis","volume":"44","author":"Pascual-Morena","year":"2024","journal-title":"Pharmacotherapy"},{"key":"ref112","doi-asserted-by":"publisher","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":"ref113","doi-asserted-by":"publisher","first-page":"7341","DOI":"10.2147\/ijgm.S369021","article-title":"Experience and perspectives in the US on the evolving treatment landscape in spinal muscular atrophy","volume":"15","author":"Ramos-Platt","year":"2022","journal-title":"Int J Gen Med"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"6501","DOI":"10.1021\/acs.jmedchem.8b00741","article-title":"Discovery of risdiplam, a selective survival of motor neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA)","volume":"61","author":"Ratni","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref115","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1002\/ana.26788","article-title":"Clinical phenotype of pediatric and adult patients with spinal muscular atrophy with four SMN2 copies: are they really all stable?","volume":"94","author":"Ricci","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.ajhg.2017.01.005","article-title":"Neurocalcin Delta suppression protects against spinal muscular atrophy in humans and across species by restoring impaired endocytosis","volume":"100","author":"Riessland","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/0959-437x(93)90093-5","article-title":"Splicing of pre-mRNA: mechanism, regulation and role in development","volume":"3","author":"Rio","year":"1993","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1083\/jcb.200304128","article-title":"Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons","volume":"163","author":"Rossoll","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s13311-020-01004-3","article-title":"Reldesemtiv in patients with spinal muscular atrophy: a phase 2 hypothesis-generating study","volume":"18","author":"Rudnicki","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1111\/ene.14567","article-title":"Sometimes they come back: new and old spinal muscular atrophy adults in the era of nusinersen","volume":"28","author":"Sansone","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1001\/jamapediatrics.2024.0492","article-title":"Clinical effectiveness of newborn screening for spinal muscular atrophy: a nonrandomized controlled trial","volume":"178","author":"Schwartz","year":"2024","journal-title":"JAMA Pediatr."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1186\/s13023-024-03442-0","article-title":"Risdiplam: therapeutic effects and tolerability in a small cohort of 6 adult type 2 and type 3 SMA patients","volume":"19","author":"Severa","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1261\/rna.7580704","article-title":"In vivo selection reveals combinatorial controls that define a critical exon in the spinal muscular atrophy genes","volume":"10","author":"Singh","year":"","journal-title":"RNA"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.bbrc.2004.01.067","article-title":"An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy","volume":"315","author":"Singh","year":"","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.bbagrm.2016.12.008","article-title":"Diverse role of survival motor neuron protein","volume":"1860","author":"Singh","year":"2017","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1128\/mcb.26.4.1333-1346.2006","article-title":"Splicing of a critical exon of human survival motor neuron is regulated by a unique silencer element located in the last intron","volume":"26","author":"Singh","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref127","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1038\/s41467-017-01559-4","article-title":"Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers","volume":"8","author":"Sivaramakrishnan","year":"2017","journal-title":"Nat. Commun."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"4114","DOI":"10.1073\/pnas.0633863100","article-title":"Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts","volume":"100","author":"Skordis","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1038\/s41591-022-01866-4","article-title":"Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the phase III SPR1NT trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat. Med."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1002\/ana.10743","article-title":"Valproic acid increases SMN levels in spinal muscular atrophy patient cells","volume":"54","author":"Sumner","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"e1010392","DOI":"10.1371\/journal.pgen.1010392","article-title":"Single-cell RNA sequencing reveals dysregulation of spinal cord cell types in a severe spinal muscular atrophy mouse model","volume":"18","author":"Sun","year":"2022","journal-title":"PLoS Genet."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"e12140","DOI":"10.1371\/journal.pone.0012140","article-title":"SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy","volume":"5","author":"Swoboda","year":"2010","journal-title":"PLoS One"},{"key":"ref133","doi-asserted-by":"publisher","first-page":"e5268","DOI":"10.1371\/journal.pone.0005268","article-title":"Phase II open label study of valproic acid in spinal muscular atrophy","volume":"4","author":"Swoboda","year":"2009","journal-title":"PLoS One"},{"key":"ref134","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.ajhg.2019.05.008","article-title":"NCALD antisense oligonucleotide therapy in addition to Nusinersen further ameliorates spinal muscular atrophy in mice","volume":"105","author":"Torres-Benito","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref135","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/nsmb.2185","article-title":"Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins","volume":"18","author":"Tripsianes","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"35ra42","DOI":"10.1126\/scitranslmed.3000830","article-title":"Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy","volume":"2","author":"Valori","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1007\/s00415-024-12188-5","article-title":"5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2","volume":"271","author":"Vill","year":"2024","journal-title":"J. Neurol."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"268","DOI":"10.20517\/jtgg.2025.56","article-title":"SMN2 as a therapeutic target in spinal muscular atrophy: advances in gene expression modulation","volume":"9","author":"Virata","year":"2025","journal-title":"J. Transl. Genet. Genom."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1212\/01.wnl.0000231139.26253.d0","article-title":"Valproate may improve strength and function in patients with type III\/IV spinal muscle atrophy","volume":"67","author":"Weihl","year":"2006","journal-title":"Neurology"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1001\/archneur.1971.00490030102014","article-title":"Two early infantile hereditary cases of progressive muscular atrophy simulating dystrophy, but on a neural basis","volume":"25","author":"Werdnig","year":"1891","journal-title":"Arch. Neurol."},{"key":"ref142","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1007\/s00439-006-0156-7","article-title":"Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number","volume":"119","author":"Wirth","year":"2006","journal-title":"Hum. Genet."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1186\/s12967-024-05661-2","article-title":"Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside","volume":"22","author":"Xu","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"e0298609","DOI":"10.1371\/journal.pone.0298609","article-title":"Exploration of adverse events associated with risdiplam use: retrospective cases from the US Food and Drug Administration adverse event reporting system (FAERS) database","volume":"19","author":"Yu","year":"2024","journal-title":"PLoS One"},{"key":"ref145","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/bf02185762","article-title":"Deletions in the SMN gene in infantile and adult spinal muscular atrophy patients from the same family","volume":"97","author":"Zappata","year":"1996","journal-title":"Hum. Genet."},{"key":"ref146","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1001\/archneur.1995.00540290108025","article-title":"Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications","volume":"52","author":"Zerres","year":"1995","journal-title":"Arch. Neurol."},{"key":"ref147","doi-asserted-by":"publisher","first-page":"1475884","DOI":"10.3389\/fphar.2024.1475884","article-title":"Comprehensive analysis of adverse events associated with onasemnogene abeparvovec (Zolgensma) in spinal muscular atrophy patients: insights from FAERS database","volume":"15","author":"Zhang","year":"2024","journal-title":"Front. Pharmacol."},{"key":"ref148","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/ejhg.2012.293","article-title":"Genome-wide analysis shows association of epigenetic changes in regulators of Rab and rho GTPases with spinal muscular atrophy severity","volume":"21","author":"Zheleznyakova","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"6265","DOI":"10.1093\/hmg\/ddv329","article-title":"Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response","volume":"24","author":"Zhou","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"112461","DOI":"10.1016\/j.isci.2025.112461","article-title":"Comprehensive analysis across SMN2 excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy","volume":"28","author":"Zwartkruis","year":"2025","journal-title":"iScience"}],"container-title":["Frontiers in Human Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2026.1833269\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:34Z","timestamp":1785217054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2026.1833269\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":150,"alternative-id":["10.3389\/fnhum.2026.1833269"],"URL":"https:\/\/doi.org\/10.3389\/fnhum.2026.1833269","relation":{},"ISSN":["1662-5161"],"issn-type":[{"value":"1662-5161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"article-number":"1833269"}}