Current and emerging targeted therapies for spinal muscular atrophy

References

• Spinal muscular atrophy. Nat Rev Dis Primers. 2022;8 1. doi: 10.1038/s41572-022-00385-3
   Web of Science ®Google Scholar
• Orthologs KE. Paralogs, and evolutionary genomics. Annu Rev Genet. 2005;39(1):309–338. doi: 10.1146/annurev.genet.39.073003.114725
   PubMedGoogle Scholar
• Dittmar K, Liberles D. Evolution after Gene Duplication. Hoboken, United states: John Wiley & Sons, Incorporated; 2010.
   Google Scholar
• Chen X, Sanchis-Juan A, French CE, et al. Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data. Genet Med. 2020;22(5):945–953. doi: 10.1038/s41436-020-0754-0
   PubMed Web of Science ®Google Scholar
• Komar AA. Single nucleotide polymorphisms. Humana, (NY); 2009.
   Google Scholar
• Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies. Brain. 2014;137(11):2879–2896. doi: 10.1093/brain/awu169
   PubMedGoogle Scholar
• Axente M, Shelby E-S, Mirea A, et al. Clinical features and genetics in non-5q spinal muscular atrophy caused by acid ceramidase deficiency. J Med Life. 2021;14(3):424–428. doi: 10.25122/jml-2021-0147
   PubMedGoogle Scholar
• Matesanz SE, Curry C, Gross B, et al. Clinical course in a patient with spinal muscular atrophy type 0 treated with Nusinersen and Onasemnogene Abeparvovec. J Child Neurol. 2020;35(11):717–723. doi: 10.1177/0883073820928784
   PubMed Web of Science ®Google Scholar
• Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clinics. 2015;33(4):831–846. doi: 10.1016/j.ncl.2015.07.004
   PubMed Web of Science ®Google Scholar
• Karimzadeh P, Najmabadi H, Lochmuller H, et al. Five patients with spinal muscular atrophy-progressive myoclonic epilepsy (SMA-PME): a novel pathogenic variant, treatment and review of the literature. Neuromuscular Disorders. 2022;32(10):806–810. doi: 10.1016/j.nmd.2022.08.002
   PubMed Web of Science ®Google Scholar
• Elsea SH, Solyom A, Martin K, et al. ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy. Human Mutation. 2020;41(9):1469–1487. doi: 10.1002/humu.24056
   PubMed Web of Science ®Google Scholar
• Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy – a literature review. Orphanet J Rare Diseases. 2017;12(1). doi: 10.1186/s13023-017-0671-8
   PubMedGoogle Scholar
• Coratti G, Ricci M, Capasso A, et al. Prevalence of spinal muscular atrophy in the era of disease-modifying therapies. Neurology. 2023;100(11):522–528. doi: 10.1212/WNL.0000000000201654
   PubMed Web of Science ®Google Scholar
• Gaviglio A, McKasson S, Singh S, et al. Infants with congenital diseases identified through newborn screening—United States, 2018–2020. Int J Neonatal Screen. 2023;9(2):23. doi: 10.3390/ijns9020023
   PubMed Web of Science ®Google Scholar
• Govoni A, Gagliardi D, Comi GP, et al. Time is motor neuron: Therapeutic Window and its correlation with pathogenetic mechanisms in spinal muscular atrophy. Mol Neurobiol. 2018;55(8):6307–6318. doi: 10.1007/s12035-017-0831-9
   PubMed Web of Science ®Google Scholar
• Vill K, Kölbel H, Schwartz O, et al. One year of newborn screening for SMA - Results of a German pilot project. J Neuromuscul Dis. 2019;6(4):503–515. doi: 10.3233/JND-190428
   PubMedGoogle Scholar
• Müller-Felber W, Blaschek A, Schwartz O, et al. Newbornscreening SMA - From pilot project to nationwide screening in Germany. J Neuromuscul Dis. 2023;10(1):55–65. doi: 10.3233/JND-221577
   PubMedGoogle Scholar
• Lee BH, Deng S, Chiriboga CA, et al. Newborn screening for spinal muscular atrophy in new York state: clinical outcomes from the first 3 years. Neurology. 2022;99(14):e1527–1537. doi: 10.1212/WNL.0000000000200986
   PubMed Web of Science ®Google Scholar
• Kariyawasam D, Russell JS, Wiley V, et al. The implementation of newborn screening for spinal muscular atrophy: the Australian experience. Genet Med. 2020;22(3):557–565. doi: 10.1038/s41436-019-0673-0
   PubMed Web of Science ®Google Scholar
• D’Silva AM, Kariyawasam DST, Best S, et al. Integrating newborn screening for spinal muscular atrophy into health care systems: an Australian pilot programme. Dev Med Child Neurol. 2022;64(5):625–632. doi: 10.1111/dmcn.15117
   PubMed Web of Science ®Google Scholar
• Hale K, Ojodu J, Singh S. Landscape of spinal muscular atrophy newborn screening in the United States: 2018–2021. Int J Neonatal Screen. 2021;7(3):33. doi: 10.3390/ijns7030033
   PubMed Web of Science ®Google Scholar
• Ricci FS, D’Alessandro R, Vacchetti M, et al. Improving recognition of treatable rare Neuromuscular Disorders in primary care: a pilot feasibility study. Children (Basel). 2022;9(7):1063. doi: 10.3390/children9071063
   PubMed Web of Science ®Google Scholar
• Matteson J, Wu CH, Mathur D, et al. California’s experience with SMA newborn screening: a successful path to early intervention. J Neuromuscul Dis. 2022;9(6):777–785. doi: 10.3233/JND-221561
   PubMedGoogle Scholar
• Calucho M, Bernal S, Alías L, et al. Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuro Disord. 2018;28(3):208–215. doi: 10.1016/j.nmd.2018.01.003
   PubMed Web of Science ®Google Scholar
• Koblan LW, Erdos MR, Wilson C, et al. In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice. Nature. 2021;589(7843):608–614. doi: 10.1038/s41586-020-03086-7
   PubMed Web of Science ®Google Scholar
• Singh RN, Howell MD, Ottesen EW, et al. Diverse role of survival motor neuron protein. Biochim Biophys Acta Gene Regul Mech. 2017;1860(3):299–315. doi: 10.1016/j.bbagrm.2016.12.008
   PubMed Web of Science ®Google Scholar
• Wang J, Dreyfuss G. Characterization of functional domains of the SMN proteinin vivo. J Biol Chem. 2001;276(48):45387–45393. doi:10.1074/jbc.M105059200
   PubMed Web of Science ®Google Scholar
• Carlini MJ, Triplett MK, Pellizzoni L, et al. Neuromuscular denervation and deafferentation but not motor neuron death are disease features in the Smn2B/- mouse model of SMA. PLoS One. 2022;17(8):e0267990. doi:10.1371/journal.pone.0267990
   PubMed Web of Science ®Google Scholar
• Tisdale S, Van Alstyne M, Simon CM, et al. SMN controls neuromuscular junction integrity through U7 snRNP. Cell Rep. 2022;40(12):111393. doi: 10.1016/j.celrep.2022.111393
   PubMed Web of Science ®Google Scholar
• Kim J-K, Jha NN, Awano T, et al. A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses. Neuron. 2023;111(9):1423–1439.e1424. doi: 10.1016/j.neuron.2023.02.004
   PubMed Web of Science ®Google Scholar
• Swoboda KJ, Prior TW, Scott CB, et al. Natural history of denervation in SMA: relation to age,SMN2 copy number, and function. Ann Neurol. 2005;57(5):704–712. doi: 10.1002/ana.20473
   PubMed Web of Science ®Google Scholar
• Canson D, Glubb D, Spurdle AB. Variant effect on splicing regulatory elements, branchpoint usage, and pseudoexonization: strategies to enhance bioinformatic prediction using hereditary cancer genes as exemplars. Human Mutation. 2020;41(10):1705–1721. doi:10.1002/humu.24074
   PubMed Web of Science ®Google Scholar
• Mount SM. Exonic splicing enhancers and exonic splicing silencers. In: Jorde LB, Little PFR, Dunn MJ, et al., editors. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. Wiley; 2005. doi 10.1002/047001153X.g402314
   Google Scholar
• Khoo B, Krainer AR. Splicing therapeutics in SMN2 and APOB. Curr Opin Mol Ther. 2009;11(2):108–115.
   PubMedGoogle Scholar
• Antonaci L, Pera MC, Mercuri E. New therapies for spinal muscular atrophy: where we stand and what is next. Eur J Pediatr. 2023;182(7):2935–2942. doi: 10.1007/s00431-023-04883-8
   PubMed Web of Science ®Google Scholar
• Bennett CF, Krainer AR, Cleveland DW. Antisense oligonucleotide therapies for neurodegenerative diseases. Annu Rev Neurosci. 2019;42(1):385–406. doi:10.1146/annurev-neuro-070918-050501
   PubMedGoogle Scholar
• Rochette C, Gilbert N, Simard L. SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens. Hum Genet. 2001;108(3):255–266. doi:10.1007/s004390100473
   PubMed Web of Science ®Google Scholar
• Hua Y, Vickers TA, Okunola HL, et al. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet. 2008;82(4):834–848. doi: 10.1016/j.ajhg.2008.01.014
   PubMed Web of Science ®Google Scholar
• Singh NN, Howell MD, Androphy EJ, et al. How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy. Genet Ther. 2017;24(9):520–526. doi: 10.1038/gt.2017.34
   PubMed Web of Science ®Google Scholar
• Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy. Neurology. 2016;86(10):890–897. doi: 10.1212/WNL.0000000000002445
   PubMed Web of Science ®Google Scholar
• Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017–3026. doi: 10.1016/S0140-6736(16)31408-8
   PubMed Web of Science ®Google Scholar
• Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723–1732. doi: 10.1056/NEJMoa1702752
   PubMed Web of Science ®Google Scholar
• Jalali A, Rothwell E, Botkin JR, et al. Cost-effectiveness of Nusinersen and universal newborn screening for spinal muscular atrophy. J Pediatr. 2020;227:274–280.e272. doi: 10.1016/j.jpeds.2020.07.033
   PubMed Web of Science ®Google Scholar
• De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study. Neuromuscular Disorders. 2019;29(11):842–856. doi: 10.1016/j.nmd.2019.09.007
   PubMed Web of Science ®Google Scholar
• Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–635. doi: 10.1056/NEJMoa1710504
   PubMed Web of Science ®Google Scholar
• Darras BT, Chiriboga CA, Iannaccone ST, et al. Nusinersen in later-onset spinal muscular atrophy: long-term results from the phase 1/2 studies. Neurology. 2019;92(21):e2492–e2506. doi: 10.1212/WNL.0000000000007527
   PubMed Web of Science ®Google Scholar
• Acsadi G, Crawford TO, Müller-Felber W, et al. Safety and efficacy of nusinersen in spinal muscular atrophy: the EMBRACE study. Muscle Nerve. 2021;63(5):668–677. doi: 10.1002/mus.27187
   PubMed Web of Science ®Google Scholar
• Nuzzo T, Russo R, Errico F, et al. Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients. Commun Med. 2023;3(1):28. doi: 10.1038/s43856-023-00256-2
   PubMedGoogle Scholar
• Hastie E, Samulski RJ. Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success–a personal perspective. Hum Gene Ther. 2015;26(5):257–265. doi:10.1089/hum.2015.025
   PubMed Web of Science ®Google Scholar
• Thomsen G, Burghes AHM, Hsieh C, et al. Biodistribution of onasemnogene abeparvovec DNA, mRNA and SMN protein in human tissue. Nat Med. 2021;27(10):1701–1711. doi: 10.1038/s41591-021-01483-7
   PubMed Web of Science ®Google Scholar
• Chand DH, Sun R, Diab KA, et al. Review of cardiac safety in onasemnogene abeparvovec gene replacement therapy: translation from preclinical to clinical findings. Genet Ther. 2023;30(9):685–697. doi: 10.1038/s41434-023-00401-5
   PubMedGoogle Scholar
• Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, et al. Current clinical applications of in vivo gene therapy with AAVs. Mol Ther. 2021;29(2):464–488. doi: 10.1016/j.ymthe.2020.12.007
   PubMed Web of Science ®Google Scholar
• Lowes LP, Alfano LN, Arnold WD, et al. Impact of age and motor function in a phase 1/2A study of infants with SMA type 1 receiving single-dose gene replacement therapy. Pediatr Neurol. 2019;98:39–45. doi: 10.1016/j.pediatrneurol.2019.05.005
   PubMed Web of Science ®Google Scholar
• Mendell JR, Al-Zaidy SA, Lehman KJ, et al. Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy. JAMA Neurol. 2021;78(7):834–841. doi: 10.1001/jamaneurol.2021.1272
   PubMed Web of Science ®Google Scholar
• Day JW, Finkel RS, Chiriboga CA, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021;20(4):284–293. doi: 10.1016/S1474-4422(21)00001-6
   PubMed Web of Science ®Google Scholar
• Mercuri E, Muntoni F, Baranello G, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021;20(10):832–841. doi: 10.1016/S1474-4422(21)00251-9
   PubMed Web of Science ®Google Scholar
• Ferrante L, Melendez-Zaidi A, Lindsey W, et al. Novel use of nusinersen as a therapeutic bridge to onasemnogene abeparvovec-xioi in a premature neonate with type 1 spinal muscular atrophy. Muscle Nerve. 2022;66(2):E8–e10. doi: 10.1002/mus.27648
   PubMed Web of Science ®Google Scholar
• Scheijmans FEV, Cuppen I, van Eijk RPA, et al. Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study. Brain Comm. 2022;4(6): doi: 10.1093/braincomms/fcac269
   PubMedGoogle Scholar
• Choudhury SR, Harris AF, Cabral DJ, et al. Widespread central nervous system gene transfer and silencing after systemic delivery of novel AAV-AS vector. Mol Ther. 2016;24(4):726–735. doi: 10.1038/mt.2015.231
   PubMed Web of Science ®Google Scholar
• Besse A, Astord S, Marais T, et al. AAV9-mediated expression of SMN restricted to neurons does not rescue the spinal muscular atrophy phenotype in mice. Mol Ther. 2020;28(8):1887–1901. doi: 10.1016/j.ymthe.2020.05.011
   PubMed Web of Science ®Google Scholar
• Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the Nervous System: a clinical reality. Neuron. 2019;101(5):839–862. doi:10.1016/j.neuron.2019.02.017
   PubMed Web of Science ®Google Scholar
• Parsons J, Kuntz NL, Brandsema J, et al. Respond: Preliminary Efficacy and Safety Data in Children with Spinal Muscular Atrophy Treated With Nusinersen After Onasemnogene Abeparvovec. 2023. https://www.mdaconference.org/abstract-library/respond-preliminary-efficacy-and-safety-data-in-children-with-spinal-muscular-atrophy-treated-with-nusinersen-after-onasemnogene-abeparvovec/
   Google Scholar
• Tosi M, Catteruccia M, Cherchi C, et al. Switching therapies: safety profile of onasemnogene abeparvovec-xioi in a SMA1 patient previously treated with Risdiplam. Acta Myol. 2022;41(3):117–120. doi: 10.36185/2532-1900-077
   PubMedGoogle Scholar
• Fox D, To TM, Seetasith A, et al. Adherence and persistence to Nusinersen for spinal muscular atrophy: a US claims-based analysis. Adv Ther. 2023;40(3):903–919. doi: 10.1007/s12325-022-02376-y
   PubMed Web of Science ®Google Scholar
• McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997;387(6628):83–90. doi:10.1038/387083a0
   PubMed Web of Science ®Google Scholar
• Joulia-Ekaza D, Cabello G. Myostatin regulation of muscle development: molecular basis, natural mutations, physiopathological aspects. Exp Cell Res. 2006;312(13):2401–2414. doi:10.1016/j.yexcr.2006.04.012
   PubMed Web of Science ®Google Scholar
• Welsh BT, Cote SM, Meshulam D, et al. Preclinical safety assessment and toxicokinetics of Apitegromab, an antibody targeting proforms of myostatin for the treatment of muscle-atrophying disease. Int J Toxicol. 2021;40(4):322–336. doi: 10.1177/10915818211025477
   PubMed Web of Science ®Google Scholar
• Barrett D, Bilic S, Chyung Y, et al. A randomized phase 1 safety, pharmacokinetic and pharmacodynamic study of the novel myostatin inhibitor apitegromab (SRK-015): a potential treatment for spinal muscular atrophy. Adv Ther. 2021;38(6):3203–3222. doi: 10.1007/s12325-021-01757-z
   PubMed Web of Science ®Google Scholar
• Collibee SE, Bergnes G, Chuang C, et al. Discovery of reldesemtiv, a fast skeletal muscle troponin activator for the treatment of impaired muscle function. J Med Chem. 2021;64(20):14930–14941. doi: 10.1021/acs.jmedchem.1c01067
   PubMed Web of Science ®Google Scholar
• Rudnicki SA, Andrews JA, Duong T, et al. Reldesemtiv in patients with spinal muscular atrophy: a phase 2 hypothesis-generating study. Neurotherapeutics. 2021;18(2):1127–1136. doi: 10.1007/s13311-020-01004-3
   PubMed Web of Science ®Google Scholar
• Gebrehiwet P, Meng L, Rudnicki SA, et al. Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS. J Med Econ. 2023;26(1):488–493. doi: 10.1080/13696998.2023.2192588
   PubMed Web of Science ®Google Scholar
• Shefner JM, Andrews JA, Genge A, et al. A phase 2, double-blind, randomized, dose-ranging trial of reldesemtiv in patients with ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021;22(3–4):287–299. doi: 10.1080/21678421.2020.1822410
   PubMed Web of Science ®Google Scholar
• Alves CRR, Ha LL, Yaworski R, et al. Base editing as a genetic treatment for spinal muscular atrophy. bioRxiv. 2023. doi: 10.1101/2023.01.20.524978
   Google Scholar
• Miccio A, Antoniou P, Ciura S, et al. Novel genome-editing-based approaches to treat motor neuron diseases: promises and challenges. Mol Ther. 2022;30(1):47–53. doi: 10.1016/j.ymthe.2021.04.003
   PubMed Web of Science ®Google Scholar
• Antoniou P, Miccio A, Brusson M. Base and prime editing technologies for blood Disorders. Frontiers In Genome Ed. 2021;3. doi: 10.3389/fgeed.2021.618406
   PubMedGoogle Scholar
• Scott DA, Zhang F. Implications of human genetic variation in CRISPR-based therapeutic genome editing. Nat Med. 2017;23(9):1095–1101. doi:10.1038/nm.4377
   PubMed Web of Science ®Google Scholar
• Garrood WT, Kranjc N, Petri K, et al. Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito. Proc Nat Acad Sci. 2021;118(22):e2004838117. doi: 10.1073/pnas.2004838117
   PubMed Web of Science ®Google Scholar
• Petri K, Kim DY, Sasaki KE, et al. Global-scale CRISPR gene editor specificity profiling by ONE-seq identifies population-specific, variant off-target effects. bioRxiv. 2021. doi: 10.1101/2021.04.05.438458
   Google Scholar
• Strauss KA, Farrar MA, Muntoni F, et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the phase III SPR1NT trial. Nat Med. 2022;28(7):1390–1397. doi: 10.1038/s41591-022-01867-3
   PubMed Web of Science ®Google Scholar
• Strauss KA, Farrar MA, Muntoni F, et al. Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the phase III SPR1NT trial. Nat Med. 2022;28(7):1381–1389. doi: 10.1038/s41591-022-01866-4
   PubMed Web of Science ®Google Scholar
• Zolgensma (onasemnogene abeparvovec-xioi) [package insert]. Cambridge, MA: Novartis Pharmaceuticals Corporation; 2019.
   Google Scholar
• Feldman AG, Parsons JA, Dutmer CM, et al. Subacute liver failure following gene replacement therapy for spinal muscular atrophy type 1. J Pediatr. 2020;225:252–258.e251. doi: 10.1016/j.jpeds.2020.05.044
   PubMed Web of Science ®Google Scholar
• Li X, Wei X, Lin J, et al. A versatile toolkit for overcoming AAV immunity. Front Immunol. 2022;13:991832. doi:10.3389/fimmu.2022.991832
   PubMed Web of Science ®Google Scholar
• Verdera HC, Kuranda K, Mingozzi F. AAV vector immunogenicity in humans: a long journey to successful gene transfer. Mol Ther. 2020;28(3):723–746. doi:10.1016/j.ymthe.2019.12.010
   PubMed Web of Science ®Google Scholar
• Chand D, Mohr F, McMillan H, et al. Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy. J Hepatol. 2021;74(3):560–566. doi: 10.1016/j.jhep.2020.11.001
   PubMed Web of Science ®Google Scholar
• Bevan AK, Hutchinson KR, Foust KD, et al. Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery. Hum Mol Genet. 2010;19(20):3895–3905. doi: 10.1093/hmg/ddq300
   PubMed Web of Science ®Google Scholar
• Shababi M, Lorson CL, Rudnik-Schoneborn SS. Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease? J Anat. 2014;224(1):15–28. doi:10.1111/joa.12083
   PubMed Web of Science ®Google Scholar
• Zinn E, Unzu C, Schmit PF, et al. Ancestral library identifies conserved reprogrammable liver motif on AAV capsid. Cell Rep Med. 2022;3(11):100803. doi: 10.1016/j.xcrm.2022.100803
   PubMedGoogle Scholar
• Ratni H, Scalco RS, Stephan AH. Risdiplam, the first approved small molecule splicing modifier drug as a blueprint for future transformative medicines. ACS Med Chem Lett. 2021;12(6):874–877. doi:10.1021/acsmedchemlett.0c00659
   PubMed Web of Science ®Google Scholar
• Sivaramakrishnan M, McCarthy KD, Campagne S, et al. Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers. Nat Commun. 2017;8(1):1476. doi: 10.1038/s41467-017-01559-4
   PubMed Web of Science ®Google Scholar
• Sturm S, Günther A, Jaber B, et al. A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br J Clin Pharmacol. 2019;85(1):181–193. doi: 10.1111/bcp.13786
   PubMed Web of Science ®Google Scholar
• Mercuri E, Deconinck N, Mazzone ES, et al. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022;21(1):42–52. doi: 10.1016/S1474-4422(21)00367-7
   PubMed Web of Science ®Google Scholar
• Kletzl H, Ajmi H, Antys I, et al. Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam. Br J Clin Pharmacol. 2022;88(8):3749–3759. doi: 10.1111/bcp.15319
   PubMed Web of Science ®Google Scholar
• Chiriboga CA, Servais L, Baranello G, et al. Safety update: risdiplam clinical trial program for spinal muscular atrophy (SMA). 2023. https://medically.gene.com/content/dam/pdmahub/restricted/neurology/mda-2023/MDA-2023-poster-chiriboga-safety-update-risdiplam-clinical-trial-program-for-spinal-muscular-atrophy.pdf
   Google Scholar
• Masson R, Mazurkiewicz-Bełdzińska M, Rose K, et al. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet Neurol. 2022;21(12):1110–1119. doi: 10.1016/S1474-4422(22)00339-8
   PubMed Web of Science ®Google Scholar
• Garzón NC Ñ, Pitarch Castellano I, Sevilla T, et al. Risdiplam in non-sitter patients aged 16 years and older with 5q spinal muscular atrophy. Muscle Nerve. 2023;67(5):407–411. doi: 10.1002/mus.27804
   PubMed Web of Science ®Google Scholar
• Harada Y, Rao VK, Arya K, et al. Combination molecular therapies for type 1 spinal muscular atrophy. Muscle Nerve. 2020;62(4):550–554. doi: 10.1002/mus.27034
   PubMed Web of Science ®Google Scholar
• Mirea A, Shelby ES, Axente M, et al. Combination therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in spinal muscular atrophy type I. J Clin Med. 2021;10(23):5540. doi: 10.3390/jcm10235540
   PubMed Web of Science ®Google Scholar
• Bitetti I, Lanzara V, Margiotta G, et al. Onasemnogene abeparvovec gene replacement therapy for the treatment of spinal muscular atrophy: a real-world observational study. Genet Ther. 2023;30(7):592–597. doi:10.1038/s41434-022-00341-6
   PubMedGoogle Scholar
• Lei Z, Meng H, Rao X, et al. Detect-seq, a chemical labeling and biotin pull-down approach for the unbiased and genome-wide off-target evaluation of programmable cytosine base editors. Nat Protoc. 2023;18(7):2221–2255. doi: 10.1038/s41596-023-00837-4
   PubMed Web of Science ®Google Scholar
• Arbab M, Matuszek Z, Kray KM, et al. Base editing rescue of spinal muscular atrophy in cells and in mice. Science. 2023;380(6642):eadg6518. doi: 10.1126/science.adg6518
   PubMed Web of Science ®Google Scholar