{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:37:33Z","timestamp":1790537853626,"version":"4.1.0"},"reference-count":331,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31NS196753"],"award-info":[{"award-number":["F31NS196753"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS060926"],"award-info":[{"award-number":["R01NS060926"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS103107"],"award-info":[{"award-number":["R21NS103107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA418685"],"award-info":[{"award-number":["MDA418685"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["MDA603852"],"award-info":[{"award-number":["MDA603852"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["DID1617"],"award-info":[{"award-number":["DID1617"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["DID1718"],"award-info":[{"award-number":["DID1718"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["MER2021"],"award-info":[{"award-number":["MER2021"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual\u2019s quality of life, independence, and lifespan. SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. The recent advent and use of genetically targeted therapies have transformed SMA into a prototype for monogenic disease treatment in the era of genetic medicine. Many SMA-affected individuals receiving these therapies achieve traditionally unobtainable motor milestones and survival rates as medicines drastically alter the natural progression of this disease. This review discusses historical SMA progression and underlying disease mechanisms, highlights advances made in therapeutic research, clinical trials, and FDA-approved medicines, and discusses possible second-generation and complementary medicines as well as optimal temporal intervention windows in order to optimize motor function and improve quality of life for all SMA-affected individuals.<\/jats:p>","DOI":"10.3390\/brainsci11020194","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T03:34:02Z","timestamp":1612496042000},"page":"194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8298-2233","authenticated-orcid":false,"given":"Kristine S.","family":"Ojala","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Reedich","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics and Physiology Program, Stanley Manne Children\u2019s Research Institute at Ann &amp; Robert H. Lurie Children\u2019s Hospital, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J.","family":"DiDonato","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics and Physiology Program, Stanley Manne Children\u2019s Research Institute at Ann &amp; Robert H. Lurie Children\u2019s Hospital, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-9726","authenticated-orcid":false,"given":"Stephen D.","family":"Meriney","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1073\/pnas.94.18.9920","article-title":"Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos","volume":"94","author":"Schrank","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/ng854","article-title":"Disruption of an SF2\/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1","volume":"30","author":"Cartegni","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","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":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fmolb.2016.00007","article-title":"Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases","volume":"3","author":"Butchbach","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy","volume":"70","author":"Feldkotter","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1086\/513913","article-title":"When is a deletion not a deletion? When it is converted","volume":"61","author":"Burghes","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","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":"ref_12","doi-asserted-by":"crossref","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":"ref_13","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.pcl.2015.03.010","article-title":"Spinal muscular atrophies","volume":"62","author":"Darras","year":"2015","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nrneurol.2015.77","article-title":"Spinal muscular atrophy--recent therapeutic advances for an old challenge","volume":"11","author":"Faravelli","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0960-8966(91)90052-T","article-title":"Workshop Report: International SMA Collaboration","volume":"1","author":"Munsat","year":"1991","journal-title":"Neuromuscul. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1177\/0883073807305673","article-title":"Spinal muscular atrophy: Clinical classification and disease heterogeneity","volume":"22","author":"Russman","year":"2007","journal-title":"J. Child Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0960-8966(99)00016-4","article-title":"59th ENMC International Workshop: Spinal Muscular Atrophies: Recent progress and revised diagnostic criteria, 17\u201319 April 1998, Soestduinen, The Netherlands","volume":"9","author":"Zerres","year":"1999","journal-title":"Neuromuscul. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","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":"ref_19","unstructured":"Sumner, C.J., Paushkin, S., and Ko, C.-P. (2017). Natural History of Spinal Muscular Atrophy. Spinal Muscular Atrophy: Disease Mechanisms and Therapy, Academic Press."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1090-3798(99)80012-9","article-title":"Very severe spinal muscular atrophy (SMA type 0): An expanding clinical phenotype","volume":"3","author":"Dubowitz","year":"1999","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1090-3798(99)80015-4","article-title":"Prenatal onset spinal muscular atrophy","volume":"3","author":"MacLeod","year":"1999","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/mus.21654","article-title":"Digital necroses and vascular thrombosis in severe spinal muscular atrophy","volume":"42","author":"Vogelgesang","year":"2010","journal-title":"Muscle Nerve"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e361","DOI":"10.1212\/NXG.0000000000000361","article-title":"Digital necrosis in an infant with severe spinal muscular atrophy","volume":"5","author":"Carrasco","year":"2019","journal-title":"Neurol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1212\/01.WNL.0000052788.39340.45","article-title":"Classical infantile spinal muscular atrophy with SMN deficiency causes sensory neuronopathy","volume":"60","author":"Goebel","year":"2003","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/jmg.2008.057950","article-title":"Congenital heart disease is a feature of severe infantile spinal muscular atrophy","volume":"45","author":"Heller","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/NEN.0000000000000144","article-title":"Spectrum of neuropathophysiology in spinal muscular atrophy type I","volume":"74","author":"Harding","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","article-title":"Spinal Muscular Atrophy","volume":"33","author":"Kolb","year":"2015","journal-title":"Neurol. Clin."},{"key":"ref_28","doi-asserted-by":"crossref","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":"ref_29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0022-510X(96)00284-5","article-title":"A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients","volume":"146","author":"Zerres","year":"1997","journal-title":"J. Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Montes, J., McDermott, M.P., Mirek, E., Mazzone, E.S., Main, M., Glanzman, A.M., Duong, T., Young, S.D., Salazar, R., and Pasternak, A. (2018). Ambulatory function in spinal muscular atrophy: Age-related patterns of progression. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199657"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1007\/s00415-008-0929-0","article-title":"A natural history study of late onset spinal muscular atrophy types 3b and 4","volume":"255","author":"Piepers","year":"2008","journal-title":"J. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e1206","DOI":"10.1212\/WNL.0000000000006241","article-title":"Patient Reported Impact of Symptoms in Spinal Muscular Atrophy (PRISM-SMA)","volume":"91","author":"Mongiovi","year":"2018","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13023-020-1339-3","article-title":"Health, wellbeing and lived experiences of adults with SMA: A scoping systematic review","volume":"15","author":"Wan","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13023-017-0695-0","article-title":"Social\/economic costs and health-related quality of life in patients with spinal muscular atrophy (SMA) in Spain","volume":"12","author":"Tizzano","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ejpn.2017.10.008","article-title":"Parents\u2019 advice to healthcare professionals working with children who have spinal muscular atrophy","volume":"22","author":"Hjorth","year":"2018","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Qian, Y., McGraw, S., Henne, J., Jarecki, J., Hobby, K., and Yeh, W.S. (2015). Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: A qualitative study. BMC Neurol., 15.","DOI":"10.1186\/s12883-015-0473-3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.clinthera.2019.03.012","article-title":"Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community","volume":"41","author":"Cruz","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"McGraw, S., Qian, Y., Henne, J., Jarecki, J., Hobby, K., and Yeh, W.S. (2017). A qualitative study of perceptions of meaningful change in spinal muscular atrophy. BMC Neurol., 17.","DOI":"10.1186\/s12883-017-0853-y"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.nmd.2017.11.004","article-title":"Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics","volume":"28","author":"Finkel","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.nmd.2017.11.005","article-title":"Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care","volume":"28","author":"Mercuri","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13023-020-01356-1","article-title":"Longitudinal natural history of type I spinal muscular atrophy: A critical review","volume":"15","author":"Mercuri","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0883073807305788","article-title":"Consensus statement for standard of care in spinal muscular atrophy","volume":"22","author":"Wang","year":"2007","journal-title":"J. Child Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study","volume":"388","author":"Finkel","year":"2016","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","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":"ref_45","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/ahg.12031","article-title":"Spinal muscular atrophy: From gene discovery to clinical trials","volume":"77","author":"Nurputra","year":"2013","journal-title":"Ann. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_47","first-page":"e8","article-title":"AVXS-101 phase 3 study in spinal muscular atrophy type 1","volume":"90","author":"Day","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","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":"ref_49","first-page":"CD006282","article-title":"Drug treatment for spinal muscular atrophy types II and III","volume":"1","author":"Wadman","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","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":"ref_51","doi-asserted-by":"crossref","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":"ref_52","doi-asserted-by":"crossref","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":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0167-4781(90)90001-I","article-title":"Structure of spliceosomal snRNPs and their role in pre-mRNA splicing","volume":"1087","author":"Luhrmann","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1073\/pnas.76.11.5495","article-title":"Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus","volume":"76","author":"Lerner","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1093\/hmg\/ddaa229","article-title":"Conditional deletion of SMN in cell culture identifies functional SMN alleles","volume":"29","author":"Blatnik","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","unstructured":"Sumner, C.J., Paushkin, S., and Ko, C.-P. (2017). The Function of Survival Motor Neuron Complex and Its Role in Spinal Muscular Atrophy Pathogenesis. Spinal Muscular Atrophy: Disease Mechanisms and Therapy, Academic Press."},{"key":"ref_57","doi-asserted-by":"crossref","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":"ref_58","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0092-8674(00)81632-3","article-title":"A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing","volume":"95","author":"Pellizzoni","year":"1998","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"31957","DOI":"10.1074\/jbc.M203478200","article-title":"Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex","volume":"277","author":"Baccon","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1093\/hmg\/8.13.2351","article-title":"Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: Implications for spinal muscular atrophy","volume":"8","author":"Buhler","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1016\/j.febslet.2005.03.034","article-title":"Unrip is a component of SMN complexes active in snRNP assembly","volume":"579","author":"Carissimi","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8126","DOI":"10.1074\/jbc.M512243200","article-title":"Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly","volume":"281","author":"Carissimi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1083\/jcb.147.6.1181","article-title":"Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems","volume":"147","author":"Charroux","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","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":"ref_65","doi-asserted-by":"crossref","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":"ref_66","doi-asserted-by":"crossref","first-page":"5631","DOI":"10.1074\/jbc.M109448200","article-title":"Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins","volume":"277","author":"Gubitz","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/ncb1101-945","article-title":"A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs","volume":"3","author":"Meister","year":"2001","journal-title":"Nat. Cell Biol"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7540","DOI":"10.1074\/jbc.M110141200","article-title":"Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component","volume":"277","author":"Pellizzoni","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1126\/science.1074962","article-title":"Essential role for the SMN complex in the specificity of snRNP assembly","volume":"298","author":"Pellizzoni","year":"2002","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","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":"ref_71","doi-asserted-by":"crossref","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":"ref_72","doi-asserted-by":"crossref","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":"ref_73","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fnana.2016.00006","article-title":"Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy","volume":"10","author":"Boido","year":"2016","journal-title":"Front. Neuroanat."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-genom-102319-103602","article-title":"Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next","volume":"21","author":"Wirth","year":"2020","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6318","DOI":"10.1093\/hmg\/ddu350","article-title":"SMN regulates axonal local translation via miR-183\/mTOR pathway","volume":"23","author":"Kye","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00418-012-0989-1","article-title":"Laminin induced local axonal translation of beta-actin mRNA is impaired in SMN-deficient motoneurons","volume":"138","author":"Rathod","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00401-011-0848-5","article-title":"The spinal muscular atrophy mouse model, SMADelta7, displays altered axonal transport without global neurofilament alterations","volume":"122","author":"Dale","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_78","doi-asserted-by":"crossref","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":"ref_79","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/nn1773","article-title":"An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance","volume":"9","author":"Yao","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","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":"ref_81","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.mcn.2009.05.009","article-title":"SMN, profilin IIa and plastin 3: A link between the deregulation of actin dynamics and SMA pathogenesis","volume":"42","author":"Bowerman","year":"2009","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"37908","DOI":"10.1074\/jbc.274.53.37908","article-title":"A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems","volume":"274","author":"Giesemann","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1096\/fj.06-7136com","article-title":"The spinal muscular atrophy gene product regulates neurite outgrowth: Importance of the C terminus","volume":"21","author":"Grothe","year":"2007","journal-title":"FASEB J."},{"key":"ref_84","doi-asserted-by":"crossref","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":"ref_85","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI72017","article-title":"Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation","volume":"124","author":"Kariya","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1523\/JNEUROSCI.5775-11.2012","article-title":"Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction","volume":"32","author":"Gogliotti","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1523\/JNEUROSCI.0204-12.2012","article-title":"Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy","volume":"32","author":"Martinez","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5524","DOI":"10.1093\/hmg\/ddv283","article-title":"SMN expression is required in motor neurons to rescue electrophysiological deficits in the SMNDelta7 mouse model of SMA","volume":"24","author":"McGovern","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Paez-Colasante, X., Seaberg, B., Martinez, T.L., Kong, L., Sumner, C.J., and Rimer, M. (2013). Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075866"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1523\/JNEUROSCI.2208-10.2010","article-title":"Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene","volume":"30","author":"Park","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1093\/hmg\/9.16.2451","article-title":"Animal models of spinal muscular atrophy","volume":"9","author":"Monani","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Gabanella, F., Butchbach, M.E., Saieva, L., Carissimi, C., Burghes, A.H., and Pellizzoni, L. (2007). Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000921"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2008.03.031","article-title":"SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing","volume":"133","author":"Zhang","year":"2008","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1093\/hmg\/ddi390","article-title":"The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation","volume":"14","author":"Gabanella","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1172\/JCI57291","article-title":"Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy","volume":"121","author":"Lutz","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/7.12.1927","article-title":"The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy","volume":"7","author":"Burlet","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/hmg\/9.3.341","article-title":"Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: An animal model for spinal muscular atrophy type III","volume":"9","author":"Jablonka","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/hmg\/ddr453","article-title":"Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy","volume":"21","author":"Ling","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/gt.2017.46","article-title":"Developmental regulation of SMN expression: Pathophysiological implications and perspectives for therapy development in spinal muscular atrophy","volume":"24","author":"Jablonka","year":"2017","journal-title":"Gene Ther."},{"key":"ref_100","unstructured":"Sumner, C.J., Paushkin, S., and Ko, C.-P. (2017). Mammalian Models of Spinal Muscular Atrophy. Spinal Muscular Atrophy: Disease Mechanisms and Therapy, Academic Press."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/hmg\/ddm379","article-title":"Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect","volume":"17","author":"Gavrilina","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1093\/hmg\/ddr275","article-title":"Temporal requirement for high SMN expression in SMA mice","volume":"20","author":"Le","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.tins.2012.04.005","article-title":"Molecular mechanisms underlying maturation and maintenance of the vertebrate neuromuscular junction","volume":"35","author":"Shi","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/ana.24332","article-title":"A large animal model of spinal muscular atrophy and correction of phenotype","volume":"77","author":"Duque","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.nmd.2011.09.007","article-title":"A critical smn threshold in mice dictates onset of an intermediate spinal muscular atrophy phenotype associated with a distinct neuromuscular junction pathology","volume":"22","author":"Bowerman","year":"2012","journal-title":"Neuromuscul. Disord."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1093\/hmg\/ddt258","article-title":"The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models","volume":"22","author":"Gogliotti","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/71709","article-title":"A mouse model for spinal muscular atrophy","volume":"24","author":"Chang","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e174","DOI":"10.1038\/mtna.2014.23","article-title":"A short antisense oligonucleotide ameliorates symptoms of severe mouse models of spinal muscular atrophy","volume":"3","author":"Keil","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/hmg\/ddi078","article-title":"SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN","volume":"14","author":"Le","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.nbd.2010.01.006","article-title":"Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy","volume":"38","author":"Michaud","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","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(-\/-) mice and results in a mouse with spinal muscular atrophy","volume":"9","author":"Monani","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1523\/JNEUROSCI.0417-15.2015","article-title":"Disease mechanisms and therapeutic approaches in spinal muscular atrophy","volume":"35","author":"Tisdale","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s40478-015-0231-1","article-title":"Transcriptional profiling of differentially vulnerable motor neurons at pre-symptomatic stage in the Smn (2b\/-) mouse model of spinal muscular atrophy","volume":"3","author":"Murray","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"E2347","DOI":"10.1073\/pnas.1613181114","article-title":"SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage","volume":"114","author":"Jangi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1101\/gr.265017.120","article-title":"LCM-seq reveals unique transcriptional adaptation mechanisms of resistant neurons and identifies protective pathways in spinal muscular atrophy","volume":"30","author":"Nichterwitz","year":"2020","journal-title":"Genome Res."},{"key":"ref_116","doi-asserted-by":"crossref","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":"ref_117","doi-asserted-by":"crossref","unstructured":"Fayzullina, S., and Martin, L.J. (2014). Skeletal muscle DNA damage precedes spinal motor neuron DNA damage in a mouse model of Spinal Muscular Atrophy (SMA). PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093329"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1080\/15476286.2014.996494","article-title":"Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: Evidence for involvement of splicing regulatory proteins","volume":"11","author":"Huo","year":"2014","journal-title":"RNA Biol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Baumer, D., Lee, S., Nicholson, G., Davies, J.L., Parkinson, N.J., Murray, L.M., Gillingwater, T.H., Ansorge, O., Davies, K.E., and Talbot, K. (2009). Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000773"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.neuron.2010.12.032","article-title":"Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy","volume":"69","author":"Mentis","year":"2011","journal-title":"Neuron"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1152\/jn.00652.2018","article-title":"Hyperexcitability precedes motoneuron loss in the Smn(2B\/-) mouse model of spinal muscular atrophy","volume":"122","author":"Quinlan","year":"2019","journal-title":"J. Neurophysiol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ling, K.K., Lin, M.Y., Zingg, B., Feng, Z., and Ko, C.P. (2010). Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015457"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/978-1-4615-0713-0_40","article-title":"The role of proprioceptive feedback in the regulation and adaptation of locomotor activity","volume":"508","author":"Lam","year":"2002","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainresbull.2007.03.010","article-title":"Muscle proprioceptive feedback and spinal networks","volume":"73","author":"Windhorst","year":"2007","journal-title":"Brain Res. Bull."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1212\/WNL.42.5.951","article-title":"Skeletal muscle tone and the misunderstood stretch reflex","volume":"42","author":"Davidoff","year":"1992","journal-title":"Neurology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1474-4422(07)70193-X","article-title":"Spastic movement disorder: Impaired reflex function and altered muscle mechanics","volume":"6","author":"Dietz","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4137\/JEN.S33122","article-title":"Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy","volume":"10","author":"Ahmad","year":"2016","journal-title":"J. Exp. Neurosci."},{"key":"ref_128","first-page":"6986","article-title":"Genetic inhibition of JNK3 ameliorates spinal muscular atrophy","volume":"24","author":"Genabai","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1016\/j.celrep.2017.12.003","article-title":"Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy","volume":"21","author":"Simon","year":"2017","journal-title":"Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Schellino, R., Boido, M., and Vercelli, A. (2019). JNK Signaling Pathway Involvement in Spinal Cord Neuron Development and Death. Cells, 8.","DOI":"10.3390\/cells8121576"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41419-019-1727-6","article-title":"Reduced P53 levels ameliorate neuromuscular junction loss without affecting motor neuron pathology in a mouse model of spinal muscular atrophy","volume":"10","author":"Courtney","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"113587","DOI":"10.1016\/j.expneurol.2020.113587","article-title":"Spinal motor neuron loss occurs through a p53-and-p21-independent mechanism in the Smn2B\/\u2212 mouse model of spinal muscular atrophy","volume":"337","author":"Reedich","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/hmg\/11.12.1439","article-title":"Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model","volume":"11","author":"Nicole","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","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":"ref_135","doi-asserted-by":"crossref","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":"ref_136","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mcn.2015.11.007","article-title":"Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice","volume":"70","author":"Neve","year":"2016","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Torres-Benito, L., Neher, M.F., Cano, R., Ruiz, R., and Tabares, L. (2011). SMN requirement for synaptic vesicle, active zone and microtubule postnatal organization in motor nerve terminals. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026164"},{"key":"ref_138","first-page":"4703","article-title":"Synaptotagmin-2, and -1, linked to neurotransmission impairment and vulnerability in Spinal Muscular Atrophy","volume":"25","author":"Tejero","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.nmd.2010.06.010","article-title":"Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for Spinal Muscular Atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing","volume":"20","author":"Voigt","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1093\/hmg\/ddw262","article-title":"Motor neuron mitochondrial dysfunction in spinal muscular atrophy","volume":"25","author":"Miller","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1242\/dmm.021766","article-title":"Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy","volume":"9","author":"Xu","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1093\/hmg\/ddu142","article-title":"Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy","volume":"23","author":"Boyer","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1523\/JNEUROSCI.4496-09.2010","article-title":"Altered intracellular Ca2+ homeostasis in nerve terminals of severe spinal muscular atrophy mice","volume":"30","author":"Ruiz","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/joa.12038","article-title":"Neurotransmitter release in motor nerve terminals of a mouse model of mild spinal muscular atrophy","volume":"224","author":"Ruiz","year":"2014","journal-title":"J. Anat."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.200703187","article-title":"Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy","volume":"179","author":"Jablonka","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1093\/hmg\/ddn189","article-title":"Embryonic motor axon development in the severe SMA mouse","volume":"17","author":"McGovern","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1093\/hmg\/ddm367","article-title":"Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy","volume":"17","author":"Murray","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Lin, T.L., Chen, T.H., Hsu, Y.Y., Cheng, Y.H., Juang, B.T., and Jong, Y.J. (2016). Selective Neuromuscular Denervation in Taiwanese Severe SMA Mouse Can Be Reversed by Morpholino Antisense Oligonucleotides. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154723"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Thomson, S.R., Nahon, J.E., Mutsaers, C.A., Thomson, D., Hamilton, G., Parson, S.H., and Gillingwater, T.H. (2012). Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052605"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0140-6736(95)90869-2","article-title":"Constitutive muscular abnormalities in culture in spinal muscular atrophy","volume":"345","author":"Braun","year":"1995","journal-title":"Lancet"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1093\/hmg\/ddn234","article-title":"SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain","volume":"17","author":"Walker","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00441-020-03236-3","article-title":"Mislocalization of SMN from the I-band and M-band in human skeletal myofibers in spinal muscular atrophy associates with primary structural alterations of the sarcomere","volume":"381","author":"Berciano","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_153","doi-asserted-by":"crossref","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. Investig."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6160","DOI":"10.1093\/hmg\/ddv332","article-title":"Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNDelta7 mouse model of SMA","volume":"24","author":"Iyer","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1046\/j.1472-8206.2001.00006.x","article-title":"On the possible role of muscle in the pathogenesis of spinal muscular atrophy","volume":"15","author":"Coupin","year":"2001","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.yexcr.2005.08.019","article-title":"Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology","volume":"311","author":"Shafey","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/labinvest.3700163","article-title":"Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients","volume":"84","author":"Arnold","year":"2004","journal-title":"Lab. Investig."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1093\/hmg\/ddu189","article-title":"Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics","volume":"23","author":"Bricceno","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ydbio.2012.05.037","article-title":"A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of survival of motor neuron protein","volume":"368","author":"Hayhurst","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1093\/hmg\/dds285","article-title":"Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models","volume":"21","author":"Osborne","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ydbio.2011.05.667","article-title":"Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons","volume":"356","author":"Lee","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1093\/hmg\/ddt612","article-title":"SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy","volume":"23","author":"Hunter","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_163","first-page":"2853","article-title":"Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy","volume":"25","author":"Hunter","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1093\/hmg\/ddv148","article-title":"Astrocytes influence the severity of spinal muscular atrophy","volume":"24","author":"Rindt","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/glia.22522","article-title":"Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production","volume":"61","author":"McGivern","year":"2013","journal-title":"Glia"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jpeds.2009.01.071","article-title":"Vascular perfusion abnormalities in infants with spinal muscular atrophy","volume":"155","author":"Araujo","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.nmd.2010.09.010","article-title":"Ultrasound evaluation of fetal movements in pregnancies at risk for severe spinal muscular atrophy","volume":"21","author":"Parra","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13023-017-0613-5","article-title":"Cardiac pathology in spinal muscular atrophy: A systematic review","volume":"12","author":"Wijngaarde","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1113\/jphysiol.2012.238196","article-title":"Physical exercise reduces cardiac defects in type 2 spinal muscular atrophy-like mice","volume":"590","author":"Biondi","year":"2012","journal-title":"J. Physiol."},{"key":"ref_170","doi-asserted-by":"crossref","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":"ref_171","first-page":"107","article-title":"ECG in neonate mice with spinal muscular atrophy allows assessment of drug efficacy","volume":"7","author":"Heier","year":"2015","journal-title":"Front. Biosci. (Elite Ed.)"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1093\/hmg\/ddq330","article-title":"Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice","volume":"19","author":"Heier","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_173","doi-asserted-by":"crossref","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":"ref_174","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/joa.12793","article-title":"Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy","volume":"232","author":"Maxwell","year":"2018","journal-title":"J. Anat."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/ejhg.2012.222","article-title":"Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585","volume":"21","author":"Schreml","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.yjmcc.2012.01.005","article-title":"Partial restoration of cardio-vascular defects in a rescued severe model of spinal muscular atrophy","volume":"52","author":"Shababi","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1093\/hmg\/ddq329","article-title":"Cardiac defects contribute to the pathology of spinal muscular atrophy models","volume":"19","author":"Shababi","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1093\/hmg\/ddx418","article-title":"Downregulation of Survivin contributes to cell-cycle arrest during postnatal cardiac development in a severe spinal muscular atrophy mouse model","volume":"27","author":"Sheng","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/mt.2014.84","article-title":"Systemic administration of a recombinant AAV1 vector encoding IGF-1 improves disease manifestations in SMA mice","volume":"22","author":"Tsai","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0387-7604(03)00075-5","article-title":"Thalamic lesions in a long-surviving child with spinal muscular atrophy type I: MRI and EEG findings","volume":"26","author":"Ito","year":"2004","journal-title":"Brain Dev."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.molmed.2012.11.002","article-title":"Spinal muscular atrophy: Going beyond the motor neuron","volume":"19","author":"Hamilton","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/joa.12083","article-title":"Spinal muscular atrophy: A motor neuron disorder or a multi-organ disease?","volume":"224","author":"Shababi","year":"2014","journal-title":"J. Anat."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00018-015-2106-9","article-title":"Is spinal muscular atrophy a disease of the motor neurons only: Pathogenesis and therapeutic implications?","volume":"73","author":"Simone","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/ana.23582","article-title":"Glucose metabolism and pancreatic defects in spinal muscular atrophy","volume":"72","author":"Bowerman","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pediatrneurol.2020.01.003","article-title":"Overturning the Paradigm of Spinal Muscular Atrophy as Just a Motor Neuron Disease","volume":"109","author":"Yeo","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1126\/science.1250127","article-title":"SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy","volume":"345","author":"Naryshkin","year":"2014","journal-title":"Science"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nbt.1610","article-title":"Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN","volume":"28","author":"Foust","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"72ra18","DOI":"10.1126\/scitranslmed.3001777","article-title":"Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy","volume":"3","author":"Passini","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/hmg\/ddr600","article-title":"A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse","volume":"21","author":"Porensky","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Chen, T.H. (2020). New and Developing Therapies in Spinal Muscular Atrophy: From Genotype to Phenotype to Treatment and Where Do We Stand?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093297"},{"key":"ref_191","unstructured":"Sumner, C.J., Paushkin, S., and Ko, C.-P. (2017). Spinal Muscular Atrophy Therapeutics Development. Spinal Muscular Atrophy: Disease Mechanisms and Therapy, Academic Press."},{"key":"ref_192","doi-asserted-by":"crossref","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":"Bertini","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/gt.2017.34","article-title":"How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy","volume":"24","author":"Singh","year":"2017","journal-title":"Gene Ther."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.4155\/fmc.15.101","article-title":"Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy","volume":"7","author":"Singh","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/aian.AIAN_298_17","article-title":"Recent Advances in Antisense Oligonucleotide Therapy in Genetic Neuromuscular Diseases","volume":"21","author":"Verma","year":"2018","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1101\/gad.1941310","article-title":"Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model","volume":"24","author":"Hua","year":"2010","journal-title":"Genes Dev."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI41615","article-title":"CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy","volume":"120","author":"Passini","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/hum.2012.211","article-title":"A novel morpholino oligomer targeting ISS-N1 improves rescue of severe spinal muscular atrophy transgenic mice","volume":"24","author":"Zhou","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1124\/jpet.113.212407","article-title":"Pharmacology of a central nervous system delivered 2\u2032-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates","volume":"350","author":"Rigo","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s13311-015-0337-y","article-title":"Spinal Muscular Atrophy Therapeutics: Where do we Stand?","volume":"12","author":"Sumner","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1172\/JCI124120","article-title":"Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment","volume":"129","author":"Ramos","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"S337","DOI":"10.1016\/j.jval.2019.04.1647","article-title":"Improved quality of life and life-years in patients with infantile-onset SMA following treatment with nusinersen","volume":"22","author":"Purser","year":"2019","journal-title":"Value Health"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","article-title":"Nusinersen in adults with 5q spinal muscular atrophy: A non-interventional, multicentre, observational cohort study","volume":"19","author":"Hagenacker","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1756286420907803","DOI":"10.1177\/1756286420907803","article-title":"Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen","volume":"13","author":"Jochmann","year":"2020","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.nbd.2015.12.014","article-title":"The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy","volume":"87","author":"Arnold","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.1016\/j.nmd.2018.06.310","article-title":"Phosphorylated neurofilament heavy chain (pNF-H) levels in infants and children with SMA: Evaluation of pNF-H as a potential biomarker of SMA disease activity","volume":"28","author":"Crawford","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/j.nmd.2018.06.028","article-title":"Association of phosphorylated neurofilament heavy chain (pNF-H) with nusinersen treatment of SMA: Analyses from the ENDEAR and CHERISH studies","volume":"28","author":"Darras","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jns.2005.03.015","article-title":"Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss","volume":"233","author":"Petzold","year":"2005","journal-title":"J. Neurol. Sci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1089\/hum.2012.225","article-title":"Antisense oligonucleotides for the treatment of spinal muscular atrophy","volume":"24","author":"Porensky","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_210","unstructured":"(2021, February 03). SPINRAZA [Package Insert], Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/209531lbl.pdf."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nn.4508","article-title":"Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy","volume":"20","author":"Corey","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.gt.3301514","article-title":"Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis","volume":"8","author":"McCarty","year":"2001","journal-title":"Gene Ther."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1038\/mt.2011.157","article-title":"Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders","volume":"19","author":"Bevan","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/hmg\/ddq514","article-title":"Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice","volume":"20","author":"Dominguez","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_215","doi-asserted-by":"crossref","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":"ref_216","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/mt.2014.210","article-title":"Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: A dose-response study in mice and nonhuman primates","volume":"23","author":"Meyer","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pediatrneurol.2019.05.005","article-title":"Impact of Age and Motor Function in a Phase 1\/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy","volume":"98","author":"Lowes","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/hum.2009.182","article-title":"Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: Implications for gene therapy using AAV vectors","volume":"21","author":"Boutin","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1172\/JCI121658","article-title":"Two breakthrough gene-targeted treatments for spinal muscular atrophy: Challenges remain","volume":"128","author":"Sumner","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_220","unstructured":"(2021, February 03). ZOLGENSMA [Package Insert], Available online: https:\/\/www.fda.gov\/media\/126109\/download."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"m580","DOI":"10.1136\/bmj.m580","article-title":"Health ministers condemn Novartis lottery for Zolgensma, the world\u2019s most expensive drug","volume":"368","author":"Dyer","year":"2020","journal-title":"BMJ"},{"key":"ref_222","doi-asserted-by":"crossref","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":"ref_223","doi-asserted-by":"crossref","first-page":"S184","DOI":"10.1016\/j.nmd.2019.06.515","article-title":"FIREFISH Part 1: 16-month safety and exploratory outcomes of risdiplam (RG7916) treatment in infants with type 1 spinal muscular atrophy","volume":"29","author":"Baranello","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1212\/WNL.94.15_supplement.1260","article-title":"SUNFISH Part 2: Efficacy and Safety of Risdiplam (RG7916) in Patients with Type 2 or Non-Ambulant Type 3 Spinal Muscular Atrophy (SMA) (1260)","volume":"94","author":"Mercuri","year":"2020","journal-title":"Neurology"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s40265-020-01410-z","article-title":"Risdiplam: First Approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"ref_226","unstructured":"Genentech Inc. (2021, February 03). Evrysdi\u2122 (Risdiplam): US Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/213535s000lbl.pdf."},{"key":"ref_227","doi-asserted-by":"crossref","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":"ref_228","unstructured":"Pagliarulo, N. (2021, February 03). Zolgensma Set a New Drug Pricing Bar. Insurers Show Some Signs of Pushback. BioPharma Dive. Available online: https:\/\/www.biopharmadive.com\/news\/zolgensma-set-a-new-drug-pricing-bar-insurers-show-some-signs-of-pushback\/558101\/."},{"key":"ref_229","first-page":"194","article-title":"Nusinersen: A Novel Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy","volume":"24","author":"Neil","year":"2019","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Chen, E., Dixon, S., Naik, R., Noone, J.M., Buchenberger, J.D., Whitmire, S.M., Mills, R., and Arnold, W. (2020). Early experiences of nusinersen for the treatment of spinal muscular atrophy: Results from a large survey of patients and caregivers. Muscle Nerve, 1\u20139.","DOI":"10.1002\/mus.27116"},{"key":"ref_231","unstructured":"Ellis, A.G., Mickle, K., Herron-Smith, S., Kumar, V.M., Cianciolo, L., Seidner, M., Thokala, P., Stevenson, M., Rind, D., and Pearson, S.D. (2019). Spinraza\u00ae and Zolgensma\u00ae for Spinal Muscular Atrophy: Effectiveness and Value, Institute for Clinical and Economic Review."},{"key":"ref_232","first-page":"1306","article-title":"Spinal Muscular Atrophy Therapies: ICER Grounds the Price to Value Conversation in Facts","volume":"25","author":"Starner","year":"2019","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1212\/WNL.0000000000006026","article-title":"Precious SMA natural history data: A benchmark to measure future treatment successes","volume":"91","author":"Darras","year":"2018","journal-title":"Neurology"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1089\/hum.2011.166","article-title":"Decreasing disease severity in symptomatic, Smn(-\/-);SMN2(+\/+), spinal muscular atrophy mice following scAAV9-SMN delivery","volume":"23","author":"Glascock","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3233\/JND-200475","article-title":"Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening\u2014Opportunity or Burden?","volume":"7","author":"Vill","year":"2020","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1177\/08830738030180080501","article-title":"Role of gabapentin in spinal muscular atrophy: Results of a multicenter, randomized Italian study","volume":"18","author":"Merlini","year":"2003","journal-title":"J. Child. Neurol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0022-510X(01)00632-3","article-title":"A placebo-controlled trial of gabapentin in spinal muscular atrophy","volume":"191","author":"Miller","year":"2001","journal-title":"J. Neurol. Sci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"6557","DOI":"10.1523\/JNEUROSCI.1536-12.2013","article-title":"The neuroprotective drug riluzole acts via small conductance Ca2+-activated K+ channels to ameliorate defects in spinal muscular atrophy models","volume":"33","author":"Dimitriadi","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/mus.10455","article-title":"Riluzole attenuates spinal muscular atrophy disease progression in a mouse model","volume":"28","author":"Haddad","year":"2003","journal-title":"Muscle Nerve"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/j.1365-2125.2010.03843.x","article-title":"Riluzole pharmacokinetics in young patients with spinal muscular atrophy","volume":"71","author":"Abbara","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"104590","DOI":"10.1016\/j.nbd.2019.104590","article-title":"TrkB agonistic antibodies superior to BDNF: Utility in treating motoneuron degeneration","volume":"132","author":"Guo","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm0497-429","article-title":"Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors","volume":"3","author":"Haase","year":"1997","journal-title":"Nat. Med."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1126\/science.8066451","article-title":"Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF","volume":"265","author":"Mitsumoto","year":"1994","journal-title":"Science"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/373344a0","article-title":"Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF","volume":"373","author":"Oppenheim","year":"1995","journal-title":"Nature"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/360757a0","article-title":"Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section","volume":"360","author":"Sendtner","year":"1992","journal-title":"Nature"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/358502a0","article-title":"Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy","volume":"358","author":"Sendtner","year":"1992","journal-title":"Nature"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.118.1.139","article-title":"Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration","volume":"118","author":"Sendtner","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.2119\/molmed.2012.00056","article-title":"IPLEX administration improves motor neuron survival and ameliorates motor functions in a severe mouse model of spinal muscular atrophy","volume":"18","author":"Murdocca","year":"2012","journal-title":"Mol. Med."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1093\/hmg\/ddr067","article-title":"Increased IGF-1 in muscle modulates the phenotype of severe SMA mice","volume":"20","author":"Wee","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/hum.2010.114","article-title":"Combination of SMN trans-splicing and a neurotrophic factor increases the life span and body mass in a severe model of spinal muscular atrophy","volume":"22","author":"Shababi","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.nbd.2011.06.021","article-title":"IGF-1 delivery to CNS attenuates motor neuron cell death but does not improve motor function in type III SMA mice","volume":"45","author":"Tsai","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3389\/fnmol.2017.00346","article-title":"BDNF\/trkB Induction of Calcium Transients through Cav2.2 Calcium Channels in Motoneurons Corresponds to F-actin Assembly and Growth Cone Formation on beta2-Chain Laminin (221)","volume":"10","author":"Dombert","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"100826","DOI":"10.1016\/j.isci.2020.100826","article-title":"R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy","volume":"23","author":"Tejero","year":"2020","journal-title":"iScience"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.phrs.2016.05.023","article-title":"Loganin possesses neuroprotective properties, restores SMN protein and activates protein synthesis positive regulator Akt\/mTOR in experimental models of spinal muscular atrophy","volume":"111","author":"Tseng","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4331\/wjbc.v1.i5.133","article-title":"Functional interactions between steroid hormones and neurotrophin BDNF","volume":"1","author":"Numakawa","year":"2010","journal-title":"World J. Biol. Chem."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"19348","DOI":"10.1073\/pnas.1319280110","article-title":"Dysregulation of synaptogenesis genes antecedes motor neuron pathology in spinal muscular atrophy","volume":"110","author":"Zhang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fncel.2018.00017","article-title":"Increasing Agrin Function Antagonizes Muscle Atrophy and Motor Impairment in Spinal Muscular Atrophy","volume":"12","author":"Boido","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3390\/ph3020345","article-title":"Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound","volume":"3","author":"Bordet","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.nmd.2020.10.008","article-title":"Long-term follow-up of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA) treated with olesoxime in the OLEOS trial","volume":"30","author":"Muntoni","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"9306","DOI":"10.1073\/pnas.151270098","article-title":"Regulation of myostatin activity and muscle growth","volume":"98","author":"Lee","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/387083a0","article-title":"Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member","volume":"387","author":"McPherron","year":"1997","journal-title":"Nature"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-5793(00)01570-2","article-title":"Dominant negative myostatin produces hypertrophy without hyperplasia in muscle","volume":"474","author":"Zhu","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"40735","DOI":"10.1074\/jbc.M206379200","article-title":"The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum","volume":"277","author":"Hill","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/hmg\/ddn426","article-title":"Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy","volume":"18","author":"Rose","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.nmd.2011.10.012","article-title":"Transgenic inactivation of murine myostatin does not decrease the severity of disease in a model of Spinal Muscular Atrophy","volume":"22","author":"Rindt","year":"2012","journal-title":"Neuromuscul. Disord."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1093\/hmg\/ddp253","article-title":"Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice","volume":"18","author":"Sumner","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/jcsm.12542","article-title":"Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy","volume":"11","author":"Zhou","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/hmg\/ddv629","article-title":"Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset","volume":"25","author":"Feng","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1074\/jbc.RA119.012293","article-title":"Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015","volume":"295","author":"Dagbay","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1093\/hmg\/ddy382","article-title":"Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy","volume":"28","author":"Long","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nm.2618","article-title":"Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases","volume":"18","author":"Russell","year":"2012","journal-title":"Nat. Med."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/mus.26017","article-title":"CK-2127107 amplifies skeletal muscle response to nerve activation in humans","volume":"57","author":"Andrews","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_273","unstructured":"Edell, S., Ferrufino, C., Thomsen, K., Hwee, D.T., Morgan, B.P., Malik, F.I., and Chin, E.R. (July, January 28). The Fast Skeletal Muscle Troponin Activator Reldesemtiv in Combination with Nusinersen Improves Muscle Function in a Mouse Model of Spinal Muscular Atrophy. Proceedings of the Cure SMA Conference, Anaheim, CA, USA."},{"key":"ref_274","unstructured":"Edell, S., Ferrufino, C., Thomsen, K., Hwee, D.T., Morgan, B.P., Malik, F.I., and Chin, E.R. (July, January 28). The Fast Skeletal Muscle Troponin Activator Reldesemtiv in Combination with SMN-C1 Improves Muscle Function in a Mouse Model of Spinal Muscular Atrophy. Proceedings of the Cure SMA Conference, Anaheim, CA, USA."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.nmd.2012.06.228","article-title":"Dysfunction of the neuromuscular junction in patients with spinal muscular atrophy type 2 and 3","volume":"22","author":"Wadman","year":"2012","journal-title":"Neuromuscul. Disord."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.nmd.2018.03.007","article-title":"Critical period of neuromuscular development: Importance for a new treatment of SMA","volume":"28","author":"Vrbova","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"10559","DOI":"10.1523\/JNEUROSCI.4629-12.2013","article-title":"Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome","volume":"33","author":"Tarr","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1113\/jphysiol.2014.276493","article-title":"Complete reversal of Lambert-Eaton myasthenic syndrome synaptic impairment by the combined use of a K+ channel blocker and a Ca2+ channel agonist","volume":"592","author":"Tarr","year":"2014","journal-title":"J. Physiol."},{"key":"ref_279","unstructured":"Ojala, K.S., Liang, M., Wipf, P., and Meriney, S.D. (July, January 28). A Novel, Peripherally-Targeted Treatment for Ameliorating the Neuromuscular Weakness Caused by Spinal Muscular Atrophy. Proceedings of the Cure SMA Conference, Anaheim, CA, USA."},{"key":"ref_280","unstructured":"Ojala, K.S., Kaufhold, C.J., Davey, M.R., Liang, M., Wipf, P., and Meriney, S.D. (2020, January 11\u201314). GV-58, a selective calcium channel gating modifier, can increase muscle strength and neurotransmission in untreated and ASO-treated SMA model mice. Proceedings of the Cure SMA Conference, Orlando, FL, USA."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1136\/jmg.2010.079004","article-title":"The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor","volume":"47","author":"Bernal","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.nmd.2011.03.009","article-title":"Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings","volume":"21","author":"Bernal","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/BF00212028","article-title":"Linkage mapping of the spinal muscular atrophy gene","volume":"93","author":"Burghes","year":"1994","journal-title":"Hum. Genet."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_285","first-page":"805","article-title":"Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy","volume":"57","author":"Cobben","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_286","first-page":"1218","article-title":"Association between Ag1-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy","volume":"55","author":"DiDonato","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/4.10.1927","article-title":"Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: Evidence of homozygous deletions of the SMN gene in unaffected individuals","volume":"4","author":"Hahnen","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/ejhg.2008.41","article-title":"Unaffected patients with a homozygous absence of the SMN1 gene","volume":"16","author":"Jedrzejowska","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"103","DOI":"10.18388\/abp.2009_2521","article-title":"Phenotype modifiers of spinal muscular atrophy: The number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease","volume":"56","author":"Jedrzejowska","year":"2009","journal-title":"Acta Biochim. Pol."},{"key":"ref_290","doi-asserted-by":"crossref","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":"ref_291","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.nmd.2017.06.559","article-title":"Longitudinal assessments in discordant twins with SMA","volume":"27","author":"Pane","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ajhg.2009.08.002","article-title":"A positive modifier of spinal muscular atrophy in the SMN2 gene","volume":"85","author":"Prior","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.a.30251","article-title":"Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2","volume":"130A","author":"Prior","year":"2004","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00439-019-01983-0","article-title":"Complete sequencing of the SMN2 gene in SMA patients detects SMN gene deletion junctions and variants in SMN2 that modify the SMA phenotype","volume":"138","author":"Ruhno","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"E1110","DOI":"10.1002\/humu.21173","article-title":"A rare SMN2 variant in a previously unrecognized composite splicing regulatory element induces exon 7 inclusion and reduces the clinical severity of spinal muscular atrophy","volume":"31","author":"Vezain","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/ddx166","article-title":"A-44G transition in SMN2 intron 6 protects patients with spinal muscular atrophy","volume":"26","author":"Wu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1212\/NXG.0000000000000386","article-title":"Analysis of FUS, PFN2, TDP-43, and PLS3 as potential disease severity modifiers in spinal muscular atrophy","volume":"6","author":"Wadman","year":"2020","journal-title":"Neurol. Genet."},{"key":"ref_298","doi-asserted-by":"crossref","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":"ref_299","doi-asserted-by":"crossref","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":"ref_300","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/brain\/awy167","article-title":"CHP1 reduction ameliorates spinal muscular atrophy pathology by restoring calcineurin activity and endocytosis","volume":"141","author":"Janzen","year":"2018","journal-title":"Brain"},{"key":"ref_301","doi-asserted-by":"crossref","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":"Schneider","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.omtm.2018.01.007","article-title":"Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse Model of Spinal Muscular Atrophy","volume":"9","author":"Alrafiah","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/j.1745-7254.2005.00145.x","article-title":"Plastins: Versatile modulators of actin organization in (patho)physiological cellular processes","volume":"26","author":"Delanote","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev.cellbio.19.111401.093127","article-title":"Actin assembly and endocytosis: From yeast to mammals","volume":"19","author":"Drubin","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0092-8674(03)00120-X","article-title":"Cellular motility driven by assembly and disassembly of actin filaments","volume":"112","author":"Pollard","year":"2003","journal-title":"Cell"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"e89970","DOI":"10.1172\/jci.insight.89970","article-title":"Plastin-3 extends survival and reduces severity in mouse models of spinal muscular atrophy","volume":"2","author":"Kaifer","year":"2017","journal-title":"JCI Insight"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1523\/JNEUROSCI.5808-11.2012","article-title":"Survival motor neuron affects plastin 3 protein levels leading to motor defects","volume":"32","author":"Hao","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_308","doi-asserted-by":"crossref","unstructured":"McGovern, V.L., Massoni-Laporte, A., Wang, X., Le, T.T., Le, H.T., Beattie, C.E., Rich, M.M., and Burghes, A.H. (2015). Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity in the 7 SMA Mouse. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132364"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1113\/JP278454","article-title":"Mechanisms of exercise-induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy-like mice","volume":"597","author":"Ng","year":"2019","journal-title":"J. Physiol."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1523\/JNEUROSCI.1245-05.2005","article-title":"Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse","volume":"25","author":"Grondard","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1523\/JNEUROSCI.3237-07.2008","article-title":"Exercise-induced activation of NMDA receptor promotes motor unit development and survival in a type 2 spinal muscular atrophy model mouse","volume":"28","author":"Biondi","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s12035-007-0027-9","article-title":"Exercise-induced neuroprotection in SMA model mice: A means for determining new therapeutic strategies","volume":"35","author":"Charbonnier","year":"2007","journal-title":"Mol. Neurobiol."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/0883073817750500","article-title":"Effects of Arm Cycling Exercise in Spinal Muscular Atrophy Type II Patients: A Pilot Study","volume":"33","author":"Bora","year":"2018","journal-title":"J. Child Neurol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.3389\/fphys.2019.01258","article-title":"Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy","volume":"10","author":"Houdebine","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1113\/JP271361","article-title":"Long-term exercise-specific neuroprotection in spinal muscular atrophy-like mice","volume":"594","author":"Chali","year":"2016","journal-title":"J. Physiol."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/mus.24568","article-title":"Resistance strength training exercise in children with spinal muscular atrophy","volume":"52","author":"Lewelt","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/mus.24527","article-title":"Training improves oxidative capacity, but not function, in spinal muscular atrophy type III","volume":"52","author":"Madsen","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_318","first-page":"CD012120","article-title":"Physical exercise training for type 3 spinal muscular atrophy","volume":"3","author":"Bartels","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1007\/s10072-020-04345-1","article-title":"Psychosocial impact of sport activity in neuromuscular disorders","volume":"41","author":"Vita","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3389\/fbioe.2019.00450","article-title":"The Effectiveness of Wearable Upper Limb Assistive Devices in Degenerative Neuromuscular Diseases: A Systematic Review and Meta-Analysis","volume":"7","author":"Gandolla","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_321","first-page":"1713","article-title":"Functional Tasks Performed by People with Severe Muscular Atrophy Using an sEMG Controlled Robotic Manipulator","volume":"2018","author":"Hagengruber","year":"2018","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1097\/BPO.0b013e31821f50b5","article-title":"Wilmington robotic exoskeleton: A novel device to maintain arm improvement in muscular disease","volume":"31","author":"Haumont","year":"2011","journal-title":"J. Pediatr. Orthop."},{"key":"ref_323","first-page":"675","article-title":"A body-powered functional upper limb orthosis","volume":"37","author":"Rahman","year":"2000","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_324","doi-asserted-by":"crossref","unstructured":"Grau, A., Morel, Y., Puig-Pey, A., and Cecchi, F. (2020). EXOtrainer Project Clinical Evaluation of Gait Training with Exoskeleton in Children with Spinal Muscular Atrophy. Advances in Robotics Research: From Lab to Market: ECHORD++: Robotic Science Supporting Innovation, Springer International Publishing.","DOI":"10.1007\/978-3-030-22327-4"},{"key":"ref_325","unstructured":"Sakaki, T., Aoki, K., Ushijima, K., and Sakuragi, M. (November, January 30). Robotic stretcher for spinal muscular atrophy patient: Preliminary tests of user controllability. Proceedings of the 10th International Conference on Ubiquitous Robots and Ambient Intelligence (URAI), Jeju, Korea."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.nmd.2017.07.007","article-title":"6MWT can identify type 3 SMA patients with neuromuscular junction dysfunction","volume":"27","author":"Pera","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1212\/WNL.0b013e3182749eca","article-title":"Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3","volume":"79","author":"Wadman","year":"2012","journal-title":"Neurology"},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/mus.25705","article-title":"Motor milestone assessment of infants with spinal muscular atrophy using the hammersmith infant neurological Exam-Part 2: Experience from a nusinersen clinical study","volume":"57","author":"Bishop","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1358\/dot.2017.53.6.2652413","article-title":"Nusinersen: Antisense oligonucleotide to increase SMN protein production in spinal muscular atrophy","volume":"53","author":"Paton","year":"2017","journal-title":"Drugs Today (Barc)"},{"key":"ref_330","unstructured":"Arnold, W.D., Severyn, S., Linsenmayer, M., Kelly, K., Bartlett, A., Tellez, M., Heintzman, S., Sterling, G., Kolb, S.J., and Elsheikh, B. (2020, January 11\u201314). NMJ Transmission Failure in Adults with Spinal Muscular Atrophy. Proceedings of the Cure SMA Conference, Orlando, FL, USA."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"9957","DOI":"10.1523\/JNEUROSCI.0163-13.2013","article-title":"ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions","volume":"33","author":"Je","year":"2013","journal-title":"J. Neurosci."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/2\/194\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:19:46Z","timestamp":1760159986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/2\/194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":331,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["brainsci11020194"],"URL":"https:\/\/doi.org\/10.3390\/brainsci11020194","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}