The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Onasemnogene Abeparvovec: First Global Approval
Abstract
Onasemnogene abeparvovec (onasemnogene abeparvovec-xioi; formerly AVXS-101; ZOLGENSMA ® ) is an adeno-associated viral vector-based gene therapy designed to deliver a functional copy of the human survival motor neuron (SMN) gene to the motor neuron cells of patients with spinal muscular atrophy (SMA). It has been developed by AveXis, a Novartis company, and was approved in May 2019 in the USA for the treatment of paediatric patients aged 14 vector genomes per kg of bodyweight, administered as a single intravenous infusion over 60 min. Regulatory assessments for this formulation of onasemnogene abeparvovec are underway in the EU and Japan; an intrathecal formulation is currently undergoing clinical development in the USA. This article summarizes the milestones in the development of onasemnogene abeparvovec leading to this first approval for the treatment of paediatric patients aged < 2 years with SMA and bi-allelic mutations in SMN1.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In 2019, Onasemnogene Abeparvovec was commercialized under the brand name of Zolgensma to treat children with the lethal motor neuron disease Spinal Muscular Atrophy (SMA) [89].”
From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [89]
Citations
Cites
1 retracted
Foust, K. D., Wang, X., McGovern, V. L., Braun, L., Bevan, A. K., Haidet, A. M., Le, T. T., Morales, P. R., Rich, M. M., Burghes, A. H. M., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1610 · Cited by 688
RetractedSingle-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
Mendell, J. R., Al-Zaidy, S., Shell, R., Arnold, W. D., Rodino-Klapac, L. R., Prior, T. W., Lowes, L., Alfano, L., Berry, K., Church, K., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1706198 · Cited by 2,381
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456
Verhaart, I. E. C., Robertson, A., Wilson, I. J., Aartsma-Rus, A., Cameron, S., Jones, C. C., Cook, S. F., & Lochmüller, H. (2017) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-017-0671-8 · Cited by 739
Research works printed but not linked: 15
- Groen EJN, Talbot K, Gillingwater TH. Advances in therapy for spinal muscular atrophy: promises and challenges. Nat Rev Neurol. 2018;14(4):214–24. · DOI
- Shorrock HK, Gillingwater TH, Groen EJN. Overview of current drugs and molecules in development for spinal muscular atrophy therapy. Drugs. 2018;78(3):293–305. · DOI
- Feldkötter M, Schwarzer V, Wirth R, et al. 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. Am J Hum Genet. 2002;70(2):358–68. · DOI
- Bevan AK, Duque S, Foust KD, et al. Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther J Am Soc Gene Ther. 2011;19(11):1971–80. · DOI · Paper page
- Foust K, Meyer K, Likhite S, et al. Extensive dose ranging study of AVXS-101 in the severe D7 SMA mouse model [abstract no. 435]. Mol Ther. 2017;25(5 Suppl 1):200–1.
- Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810–7. · DOI
- 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. https://doi.org/10.1016/j.pediatrneurol.2019.05.005 . · DOI · Paper page
- Dabbous O, Maru B, Jansen JP, et al. Survival, motor function, and motor milestones: comparison of AVXS-101 relative to nusinersen for the treatment of infants with spinal muscular atrophy type 1. Adv Ther. 2019;36(5):1164–76. · DOI
- Malone DC, Dean R, Arjunji R, et al. Cost-effectiveness analysis of using onasemnogene abeparvocec (AVXS-101) in spinal muscular atrophy type 1 patients. J Mark Access Health Policy. 2019;7(1):1601484. · DOI
- Mendell JR, Al-Zaidy S, Shell R, et al. AVXS-101 phase 1 gene replacement therapy clinical trial in spinal muscular atrophy type 1 (SMA1): 24-month event-free survival and achievement of developmental milestones [abstract no. OR005]. Hum Gene Ther. 2018;29(12):A22.
- Al-Zaidy S, Pickard AS, Kotha K, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019;54(2):179–85. · DOI · Paper page
- Mendell JR, Lehman KJ, McColly M, et al. AVXS-101 gene-replacement therapy (GRT) in spinal muscular atrophy type 1 (SMA1): long-term follow-up from the phase 1 clinical trial [abstract no. S25.006 plus presentation]. Neurology. 2019;92(15 Suppl). · DOI
- Day JW, Chiriboga CA, Crawford TO, et al. AVXS-101 gene-replacement therapy (GRT) for spinal muscular atrophy type 1 (SMA1): pivotal phase 3 study (STR1VE) update [abstract no. P1.6-058 plus poster]. Neurology. 2019;92(15 Suppl). · DOI
- Finkel RS, Day JW, Darras BT, et al. Phase 1 study of intrathecal administration of AVXS-101 gene-replacement therapy (GRT) for spinal muscular atrophy type 2 (SMA2) (STRONG) [abstract no. P1.6-059 plus poster]. Neurology. 2019;92(15 Suppl). · DOI
- Schultz M, Swoboda K, Farrar M, et al. AVXS-101 gene-replacement therapy (GRT) in presymptomatic spinal muscular atrophy (SMA): study update [abstract no. P1.6-057 plus poster]. Neurology. 2019;92(15 Suppl). · DOI
Cited by
Sorted by citations
AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
Costa Verdera, H., Kuranda, K., & Mingozzi, F. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.12.010 · Cited by 641
Human Immune Responses to Adeno-Associated Virus (AAV) Vectors
Ronzitti, G., Gross, D.-A., & Mingozzi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00670 · Cited by 357
The approved gene therapy drugs worldwide: from 1998 to 2019
Ma, C.-C., Wang, Z.-L., Xu, T., He, Z.-Y., & Wei, Y.-Q. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107502 · Cited by 310
Nucleic acid delivery for therapeutic applications
Gupta, A., Andresen, J. L., Manan, R. S., & Langer, R. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113834 · Cited by 351
Bucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242
Wirth, B., Karakaya, M., Kye, M. J., & Mendoza-Ferreira, N. (2020) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-102319-103602 · Cited by 267
Overcoming innate immune barriers that impede AAV gene therapy vectors
Muhuri, M., Maeda, Y., Ma, H., Ram, S., Fitzgerald, K. A., Tai, P. W. L., & Gao, G. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143780 · Cited by 212
Adeno-associated virus capsid assembly is divergent and stochastic
Wörner, T. P., Bennett, A. D., Habka, S., Snijder, J., Friese, O. V., Powers, T. W., Agbandje‐McKenna, M., & Heck, A. J. R. (2021) · Nature Communications · doi:10.1038/s41467-021-21935-5 · Cited by 228
Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery
Nidetz, N. F., McGee, M. C., Tse, L. V., Li, C., Cong, L., Li, Y., & Huang, W. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107453 · Cited by 174
“These successes led to the licensing of rAAV-based products in Europe, Glybera in 2012, and the United States, LUXTURNA in 2017 and ZOLGENSMA in 2019, as treatments for LPLD, IRD, and SMA, respectively (Buning, 2013; Hoy, 2019).”
BackgroundViral Vectors in Gene Therapy: Where Do We Stand in 2023?
Lundstrom, K. H. (2023) · Viruses · doi:10.3390/v15030698 · Cited by 208
“The AAV ‐ based Onasemnogene aboparvovec (Zolgensma) has been approved for the treatment of SMA [232].”
Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions
Weber, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.658399 · Cited by 162
Oligonucleotide Therapeutics: From Discovery and Development to Patentability
Moumné, L., Marie, A.-C., & Crouvezier, N. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020260 · Cited by 169
“However, this success is likely to be mitigated by the market access of two competing drugs: onasemnogene abeparvovec/Zolgensma [28] and risdiplam/Evrysdi [29] approved in May 2019 and August 2020, respectively.”
BackgroundAAV vectors applied to the treatment of CNS disorders: Clinical status and challenges
Kang, L., Jin, S., Wang, J., Lv, Z., Xin, C., Tan, C., Zhao, M., Wang, L., & Liu, J. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.01.067 · Cited by 131
Current clinical applications of AAV-mediated gene therapy
Byrne, B. J., Flanigan, K. M., Matesanz, S. E., Finkel, R. S., Waldrop, M. A., D'Ambrosio, E. S., Johnson, N. E., Smith, B. K., Bönnemann, C. G., Carrig, S., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.045 · Cited by 152
“108,109 Additionally, most of the mutations associated with LGMDs are missense mutations, which typically result in proteins that are present but altered in function.”
Base editing rescue of spinal muscular atrophy in cells and in mice
Arbab, M., Matuszek, Ż., Kray, K. M., Du, A., Newby, G. A., Blatnik, A. J., Raguram, A., Richter, M. F., Zhao, K. T., Levy, J. M., et al. (2023) · Science · doi:10.1126/science.adg6518 · Cited by 144
“Upregulation of SMN protein can rescue motor function and substantially improve the prognosis of SMA patients(13-15).”
BackgroundInhibition of RNA-binding proteins with small molecules
Wu, P. (2020) · Nature Reviews Chemistry · doi:10.1038/s41570-020-0201-4 · Cited by 130
Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy
Tarach, P., & Janaszewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062912 · Cited by 141
“In relation to the use of adeno-associated virus (AAV) in clinical trials, remarkable results have been reported in the treatment of spinal muscular atrophy with adeno-associated viral vector-based gene therapy using Zolgensma, which ultimately made it possible to stop the progression of the disease and, with appropri…”
MethodWeiß, C., Ziegler, A., Becker, L.-L., Johannsen, J., Brennenstuhl, H., Schreiber, G., Flotats-Bastardas, M., Stoltenburg, C., Hartmann, H., Illsinger, S., et al. (2021) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(21)00287-x · Cited by 128
Gene therapy: a double-edged sword with great powers
Tang, R., & Xu, Z. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03834-3 · Cited by 117
Capsid-specific removal of circulating antibodies to adeno-associated virus vectors
Bertin, B., Veron, P., Leborgne, C., Deschamps, J.-Y., Moullec, S., Fromes, Y., Collaud, F., Boutin, S., Latournerie, V., van Wittenberghe, L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-57893-z · Cited by 100
Intracellular trafficking of adeno-associated virus (AAV) vectors: challenges and future directions
Riyad, J. M., & Weber, T. (2021) · Gene Therapy · doi:10.1038/s41434-021-00243-z · Cited by 124
Zhao, H., Lee, K.-J., Daris, M., Lin, Y., Wolfe, T., Sheng, J., Plewa, C., Wang, S., & Meisen, W. H. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.004 · Cited by 98
Abati, E., Bresolin, N., Comi, G. P., & Corti, S. P. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1738390 · Cited by 107
“Furthermore, in 2019, onasemnogene abeparvovec (trade name Zolgensma), an AAV9-based gene therapy designed to deliver a functional copy of the human survival motor neuron (SMN) gene to motor neurons, was approved by the FDA for the treatment of SMA in patients aged <2 years [98].”
BackgroundSmall molecule recognition of disease-relevant RNA structures
Meyer, S. M., Williams, C. C., Akahori, Y., Tanaka, T., Aikawa, H., Tong, Y., Childs‐Disney, J. L., & Disney, M. D. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00560f · Cited by 159
Mashel, T. V., Tarakanchikova, Y. V., Muslimov, A. R., Zyuzin, M. V., Timin, A. S., Lepik, K. V., & Fehse, B. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120282 · Cited by 102
Novel targeted therapies for Parkinson’s disease
Ntetsika, T., Papathoma, P.-E., & Markaki, I. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00279-2 · Cited by 120
“2017) confirmed the safety and efficacy of treatment, and Zolgensma→ was the first gene therapy to be approved in 2019 (Hoy 2019).”
BackgroundMitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases
Stanga, S., Caretto, A., Boido, M., & Vercelli, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103719 · Cited by 90
AAV ablates neurogenesis in the adult murine hippocampus
Johnston, S., Parylak, S. L., Kim, S., Mac, N., Lim, C., Gallina, I., Bloyd, C., Newberry, A., Saavedra, C. D., Novak, O., et al. (2021) · eLife · doi:10.7554/elife.59291 · Cited by 87
Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app
van Konijnenburg, E. M. M. H., Wortmann, S. B., Koelewijn, M. J., Tseng, L. A., Houben, R. F. A., Stöckler‐Ipsiroglu, S., Ferreira, C. R., & van Karnebeek, C. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01727-2 · Cited by 121
“In parallel, rare disease and (tailored) genetic therapies are gaining mainstream attention with the Food and Drug Administration (FDA) approval of the antisense oligonucleotide (Nusinersen) as well as the gene therapy (onasemnogene abeparvovec) for Spinal muscular atrophy (SMA) [34, 35] and the first personalized ant…”
BackgroundNucleic Acid Drugs—Current Status, Issues, and Expectations for Exosomes
Yamada, Y. (2021) · Cancers · doi:10.3390/cancers13195002 · Cited by 92
“In contrast, a gene therapy drug, onasemnogene abeparvovec (brand name, Zolgensma), which is administered via the AAV vectors encoding the normal SMN1 gene, was approved by the FDA in 2019 [107,108].”
BackgroundCan Adeno-Associated Viral Vectors Deliver Effectively Large Genes?
Tornabene, P., & Trapani, I. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.220 · Cited by 76
Abati, E., Manini, A., Comi, G. P., & Corti, S. P. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04408-w · Cited by 85
Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy
Stevens, D. L., Claborn, M. K., Gildon, B. L., Kessler, T. L., & Walker, C. K. (2020) · Annals of Pharmacotherapy · doi:10.1177/1060028020914274 · Cited by 107
Approved and marketed nanoparticles for disease targeting and applications in COVID-19
Abdellatif, A. A. H., & Alsowinea, A. F. (2021) · Nanotechnology Reviews · doi:10.1515/ntrev-2021-0115 · Cited by 105
Bouazzaoui, A., Abdellatif, A. A. H., Al-Allaf, F. A., Bogari, N. M., Al-Dehlawi, S., & Qari, S. H. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020140 · Cited by 92
Müller‐Felber, W., Vill, K., Schwartz, O., Gläser, D., Nennstiel, U., Wirth, B., Burggraf, S., Röschinger, W., Becker, M., Durner, J., et al. (2020) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-200475 · Cited by 73
From Junk to Function: LncRNAs in CNS Health and Disease
Policarpo, R., Sierksma, A. S. R., Strooper, B. D., & d’Ydewalle, C. V. O. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.714768 · Cited by 63
“AAV approaches can lead to clinical successes for devastating neurological diseases (Hoy, 2019).”
BackgroundManini, A., Abati, E., Nuredini, A., Corti, S. P., & Comi, G. P. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.814174 · Cited by 76
Gene Therapy for Duchenne Muscular Dystrophy
Elangkovan, N., & Dickson, G. (2021) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-210678 · Cited by 215
Glial cells involvement in spinal muscular atrophy: Could SMA be a neuroinflammatory disease?
Abati, E., Citterio, G., Bresolin, N., Comi, G. P., & Corti, S. P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104870 · Cited by 72
Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review
Wan, H. W. Y., Carey, K. A., D’Silva, A., Vucic, S., Kiernan, M. C., Kasparian, N. A., & Farrar, M. A. (2020) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-020-1339-3 · Cited by 72
Jablonka, S., Hennlein, L., & Sendtner, M. (2022) · Neurological Research and Practice · doi:10.1186/s42466-021-00162-9 · Cited by 79
“It appeared to be well tolerated in patients with SMA type 1 or 2 and pre-symptomatic SMA infants [125].”
BackgroundRecent Advance of Liposome Nanoparticles for Nucleic Acid Therapy
Gao, Y., Liu, X., Chen, N., Yang, X., & Tang, F. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010178 · Cited by 66
“atrophy (SMA), was approved by the FDA, further stirring up research on nucleic acid drugs [14].”
BackgroundAslesh, T., & Yokota, T. (2022) · Cells · doi:10.3390/cells11030417 · Cited by 68
“An interventional phase III, open-label trial (STRIVE, NCT03306277) with 22 SMA type 1 patients (age < 6 months) received an intravenous dose of onasemnogene [12,81].”
BackgroundFischell, J. M., & Fishman, P. S. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.747726 · Cited by 66
“Zolgensma R , for example, uses a CBA promoter (Hoy, 2019).”
BackgroundMarrone, L., Marchi, P. M., & Azzouz, M. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2012148 · Cited by 56
Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB
Kimura, S., & Harashima, H. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121216 · Cited by 65
“Actually, the AAV9 serotype is used as a vector in gene therapy for the treatment of SMA, Zolgensma, as mentioned above.”
BackgroundInfluentialFetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice
Rashnonejad, A., Chermahini, G. A., Gündüz, C., Önay, H., Aykut, A., Durmaz, B., Baka, M., Su, Q., Gao, G., & Özkınay, F. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.08.017 · Cited by 63
“These studies finally led to the first FDA-approved AAV-based gene therapy treatment for this disease.(15) With these promising advancements in the field of gene therapy, we thought that the next step could be testing gene therapy treatments in an earlier developmental stage, specifically, for severe types of SMA (typ…”
BackgroundRational engineering of a functional CpG-free ITR for AAV gene therapy
Pan, X., Yue, Y., Boftsi, M., Wasala, L. P., Tran, N. T., Zhang, K., Pintel, D. J., Tai, P. W. L., & Duan, D. (2022) · Gene Therapy · doi:10.1038/s41434-021-00296-0 · Cited by 53
Ye, D., Chukwu, C., Yang, Y., Hu, Z., & Chen, H. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115363 · Cited by 60
López-Gordo, E., Chamberlain, K., Riyad, J. M., Kohlbrenner, E., & Weber, T. (2024) · Viruses · doi:10.3390/v16030442 · Cited by 68
“In 2017, the FDA approved LUXTURNA TM (AAV2-based) for correcting Leber Congenital Amaurosis type 2 (LCA2) [71,72] and approved ZOLGENSMA TM (AAV9-based) in 2019 to treat children affected by Spinal Muscular Atrophy (SMA) [73,74].”
BackgroundMuhuri, M., Zhan, W., Maeda, Y., Li, J., Lotun, A., Chen, J., Sylvia, K., Dasgupta, I., Arjomandnejad, M., Nixon, T., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.674242 · Cited by 50
Challenges and strategies for the delivery of biologics to the cornea
Wels, M., Roels, D., Raemdonck, K., Smedt, S. C. D., & Sauvage, F. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.04.008 · Cited by 53
Wagner, H. J., Weber, W., & Fussenegger, M. (2021) · Advanced Science · doi:10.1002/advs.202004018 · Cited by 52
Current Status, Issues and Future Prospects of Personalized Medicine for Each Disease
Yamamoto, Y., Kanayama, N., Nakayama, Y., & Matsushima, N. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12030444 · Cited by 70
“There have been many gene therapy approaches in recent years to modify viral vectors such as adenoassociated virus (AAV) to supplement normal genes [13], and Onasemnogene abeparvovec (Zolgensma) was approved in 2019 for the treatment of spinal muscular atrophy (SMA) [14].”
BackgroundInfluentialKolesnik, V. V., Nurtdinov, R. F., Oloruntimehin, E. S., Karabelsky, A. V., & Malogolovkin, A. S. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1607 · Cited by 53
Tanaka, H., Sakurai, Y., Anindita, J., & Akita, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.001 · Cited by 56
Gusset, N., Stalens, C., Stumpe, E., Klouvi, L., Méjat, A., Ouillade, M.-C., & de Lemus, M. (2021) · Neuromuscular Disorders · doi:10.1016/j.nmd.2021.01.012 · Cited by 51
Kachanov, A., Kostyusheva, A., Brezgin, S., Karandashov, I., Ponomareva, N. I., Tikhonov, A., Lukashev, A. N., Pokrovsky, V. S., Zamyatnin, A. A., Parodi, A., et al. (2024) · Medicinal Research Reviews · doi:10.1002/med.22036 · Cited by 44
Cryo-electron Microscopy of Adeno-associated Virus
Stagg, S. M., Yoshioka, C., Davulcu, O., & Chapman, M. S. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00936 · Cited by 48
Besse, A., Astord, S., Marais, T., Roda, M., Giroux, B., Lejeune, F., Relaix, F., Smeriglio, P., Barkats, M., & Biferi, M. G. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.05.011 · Cited by 53
“Molec This is an open access article under the CC BY-NC-N has approved a therapeutic approach based on the stable replacement of SMN1 using viral vectors, called onasemnogene abeparvovec (Zolgensma).(9,10)”
MethodHuang, L., Wan, J., Wu, Y., Tian, Y., Yao, Y., Yao, S., Ji, X., Wang, S., Su, Z., & Xu, H. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119142 · Cited by 49
Nusinersen: A Review in 5q Spinal Muscular Atrophy
Hoy, S. M. (2021) · CNS Drugs · doi:10.1007/s40263-021-00878-x · Cited by 50
Self-citationAdeno‐associated virus (AAV)-based gene therapy for glioblastoma
Xu, X., Chen, W., Zhu, W., Chen, J., Ma, B., Ding, J., Wang, Z., Li, Y., Wang, Y., & Zhang, X. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01776-4 · Cited by 43
Revising, Correcting, and Transferring Genes
Cwik, B. (2020) · The American Journal of Bioethics · doi:10.1080/15265161.2020.1783024 · Cited by 36
“Multiple different therapeutic options already exist, for instance, for the most serious form of spinal muscular atrophy (SMA), including a neonatal gene therapy (Hoy 2019) and pharmaceutical interventions (Scoto et al. 2017).”
BackgroundLagae, L., Proesmans, M., van den Hauwe, M., Vermeulen, F. L., Waele, L. D., & Boon, M. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2024.1366943 · Cited by 41
Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders
Shah, S., Dooms, M. M., Amaral‐Garcia, S., & Igoillo‐Esteve, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.768023 · Cited by 50
“This is the case of onasemnogene abeparvovec (Zolgensma®), which, if administered early in life seems to cure spinal muscular atrophy (Hoy, 2019).”
BackgroundBosio, C. G. P., Bettiol, V. L., Alencar‐Silva, T., Franco, O. L., Pogue, R. E., Carvalho, J. L., & Felipe, M. S. S. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.02.006 · Cited by 39
Brooks, P., Ottinger, E., Portero, D., Lomash, R. M., Alimardanov, A., Terse, P., Xu, X., Chandler, R., Hauserman, J., Esposito, E., et al. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.259 · Cited by 33
“Food and Drug Administration (FDA) has now approved gene therapy products for treating an RPE65 mutation-associated retinal disease, Leber congenital amaurosis,(3) and a neurodegenerative disease, spinal muscular atrophy.(4)”
BackgroundZappa, G., LoMauro, A., Baranello, G., Cavallo, E., Corti, P., Mastella, C., & Costantino, M. A. (2021) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-021-09355-4 · Cited by 36
Adeno-Associated Virus (AAV-DJ)—Cryo-EM Structure at 1.56 Å Resolution
Xie, Q., Yoshioka, C., & Chapman, M. S. (2020) · Viruses · doi:10.3390/v12101194 · Cited by 30
“Three decades of development have culminated in the use of recombinant forms as vectors for the first FDA-approved in vivo gene therapies of genetic diseases, most notably in 2019 for a treatment of spinal muscular atrophy (SMA) [17,18].”
BackgroundUpdated review of therapeutic strategies for Charcot-Marie-Tooth disease and related neuropathies
Pisciotta, C., Saveri, P., & Pareyson, D. (2021) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2021.1935242 · Cited by 34
“This is also true for repeat gene silencing approaches, like those with ASOs and siRNAs, as for ATTRv and SMA, which however are lethal diseases as compared to most CMT forms which do not shorten the life span.”
BackgroundInfluentialEfficacy of risdiplam in spinal muscular atrophy: A systematic review and meta‐analysis
Pascual-Morena, C., Martínez-Vizcaíno, V., Cavero-Redondo, I., Martínez-García, I., Moreno-Herráiz, N., Álvarez-Bueno, C., & Saz-Lara, A. (2023) · Pharmacotherapy · doi:10.1002/phar.2866 · Cited by 28
Kok, C., Tsurusaki, S., Cabanes‐Creus, M., Igoor, S., Rao, R., Skelton, R. J. P., Liao, S. H. Y., Ginn, S. L., Knight, M., Scott, S., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.08.010 · Cited by 32
Genome Editing for CNS Disorders
Duarte, F. T., & Déglon, N. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.579062 · Cited by 36
“, 2017), and spinal muscular atrophy (SMA) with Zolgensma (a rAAV9 encoding the survival motor neuron 1 protein; Hoy, 2019) provide examples of approved products.”
BackgroundAartsma-Rus, A. M., van Roon‐Mom, W., Lauffer, M. C., Siezen, C. L. E., Duijndam, B., Roo, T. C.-D., Schüle, R., Synofzik, M., & Graeßner, H. (2023) · RNA · doi:10.1261/rna.079540.122 · Cited by 32
Gene Transfer Therapy for Neurodevelopmental Disorders
Özlü, C., Bailey, R. M., Sinnett, S. E., & Goodspeed, K. (2021) · Developmental Neuroscience · doi:10.1159/000515434 · Cited by 31
Anti-ageing gene therapy: Not so far away?
Vaiserman, A. M., FALCO, E. D., Koliada, A. K., Maslova, O., & Balistreri, C. R. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100977 · Cited by 33
Harkins, A. L., Ambegaokar, P. P., & Keeler, A. M. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00435 · Cited by 36
Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches
Mijanović, O., Branković, A., Borovjagin, A. V., Butnaru, D. V., Bezrukov, E. A., Sukhanov, R. B., Shpichka, A. I., Timashev, P. S., & Ulasov, I. V. (2020) · Viruses · doi:10.3390/v12040460 · Cited by 32
“In contrast to the majority of viral vectors utilized for gene therapy interventions, AAV-based vectors exhibit the highest potential and success rate in the treatment of several monogenic diseases, as demonstrated by clinical trials [64,65].”
BackgroundVillalón, E., Kline, R., Smith, C. E., Lorson, Z. C., Osman, E. Y., O’Day, S., Murray, L. M., & Lorson, C. L. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz188 · Cited by 31
“The most recent FDA approved therapeutic, Zolgensma, in contrast, employs a gene replacement approach in order to restore SMN expression (9).”
BackgroundConsiderations for Systemic Use of Gene Therapy
Byrne, B. J., Corti, M., & Muntoni, F. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.01.016 · Cited by 23
Vandamme, C., Xicluna, R., Hesnard, L., Devaux, M., Jaulin, N., Guilbaud, M., Le Duff, J., Couzinié, C., Moullier, P., Saulquin, X., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03110 · Cited by 23
Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges
Haque, U. S., & Yokota, T. (2024) · Genes · doi:10.3390/genes15080999 · Cited by 27
“Two other patients had asymptomatic AST and ALT elevations that resolved without intervention [81,82].”
BackgroundInfluentialCurrent non-invasive strategies for brain drug delivery: overcoming blood–brain barrier transport
Zheng, X., Yang, J., Hou, Y., Fang, Y., Wu, K., Song, Y., Liu, K., & Zhu, J. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08968-3 · Cited by 27
“The first successful AAV-based gene therapy for a CNS disorder (NCT03955679) is onasemnogene abe-parvovec (Zolgensma) approved for the treatment of paediatric patients aged 2 years with spinal muscular atrophy (SMA) by FDA [54].”
Thimm, A., Brakemeier, S., Kizina, K., Rosales, J. M., Stolte, B., Totzeck, A., Deuschl, C., Kleinschnitz, C., & Hagenacker, T. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.812063 · Cited by 28
Adeno-associated virus therapies: Pioneering solutions for human genetic diseases
Liu, D., Tian, L., Liu, L., Che, X., Li, X., Liu, C., & Wu, G. (2024) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2024.09.003 · Cited by 29
Hidden regulators: the emerging roles of lncRNAs in brain development and disease
Alammari, F., Al-Hujaily, E. M., Alshareeda, A. T., Albarakati, N., & Al-Sowayan, B. S. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1392688 · Cited by 29
“Moreover, another AAV-based therapy targeting SMN gene, called Onasemnogene abeparvovec, is the first gene therapy for SMA approved in the United States and proves that AAV methods are effective in treating neurological diseases (Hoy, 2019).”
BackgroundGene therapy in pediatrics – Clinical studies and approved drugs (as of 2023)
Gol, T. M., Zahedipour, F., Trosien, P., Ureña-Bailén, G., Kim, M., Antony, J. S., & Mezger, M. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122685 · Cited by 30
Yang, D., Ruan, Y., & Chen, Y. (2023) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.16340 · Cited by 31
Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders
Limia, C. E. G., Baird, M., Schwartz, M., Saxena, S., Meyer, K., & Wein, N. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12121979 · Cited by 28
“Survival has also been extended well beyond the two-year life expectancy [166].”
BackgroundChong, L. C., Gandhi, G., Lee, J. M., Yeo, W. W. Y., & Choi, S. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168962 · Cited by 23
“Given its effectiveness in resolving the SMA molecular defect, it adversely affects the liver by increasing the level of serum aminotransferase, a liver enzyme [7,101,102].”
BackgroundSystemic Treatment of Fabry Disease Using a Novel AAV9 Vector Expressing α-Galactosidase A
Biferi, M. G., Cohen-Tannoudji, M., García-Silva, A., Souto-Rodríguez, O., Viéitez, I., Millán, B. S., Fernández‐Carrera, A., Pérez-Márquez, T., Teijeira, S., Barrera, S., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.10.016 · Cited by 26
Suriano, C. M., Kumar, N., Verpeut, J. L., Ma, J., Jung, C., Dunn, C. E., Carvajal, B. V., Nguyen, A. V., & Boulanger, L. M. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.036 · Cited by 21
“…clinically to restore endogenous protein function in the nervous system to treat Leber ’ s congenital amaurosis 2 2,3 and spinal muscular atrophy, 4,5 and AAV-based clinical trials are under way to treat numerous other disorders of the nervous system, including Alzheimer ’ s disease, Canavan ’ s…”
Targeted-Deletion of a Tiny Sequence via Prime Editing to Restore SMN Expression
Zhou, M., Tang, S., Duan, N., Xie, M., Li, Z., Feng, M., Wu, L., Hu, Z., & Liang, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147941 · Cited by 28
“Risdiplam, Spinraza, and onasemnogene abeparvovec, which are drugs based on these approaches, have been approved by the US Food and Drug Administration (FDA) for SMA treatment [32,38,39].”
BackgroundJohannsen, J., Fuhrmann, L., Grolle, B., Morgenstern, L., Wiegand‐Grefe, S., & Denecke, J. (2020) · Health and Quality of Life Outcomes · doi:10.1186/s12955-020-01467-0 · Cited by 27
Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy
Bagga, P., Singh, S., Ram, G., Kapil, S., & Singh, A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1368658 · Cited by 20
Soini, V., Schreiber, G., Wilken, B., & Hell, A. K. (2023) · Children · doi:10.3390/children10060998 · Cited by 19
Flexible endoscopic evaluation of swallowing in children with type 1 spinal muscular atrophy
Zang, J., Johannsen, J., Denecke, J., Weiss, D., Koseki, J., Niessen, A. C., Müller, F., Nienstedt, J. C., Flügel, T., & Pflug, C. (2022) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-022-07685-0 · Cited by 22
Meng, Y., Sun, D., Qin, Y., Dong, X., Luo, G., & Liu, Y. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.019 · Cited by 32
Metadata
- Authors
- Hoy, S. M.
- Affiliations
- Springer Nature (New Zealand) (NZ)
- Corresponding author
- Hoy, Sheridan M.
- Venue
- Drugs
- Published
- 2019-07
- Volume
- 79
- Issue
- 11
- Pages
- 1255-1262
- ISSN
- 0012-6667 (ISSN-L)
- 1179-1950
- OpenAlex
- W2955699452
- Cited by
- 337
- References
- 0
- Citations by year
- 2026: 31 · 2025: 36 · 2024: 54 · 2023: 42 · 2022: 38 · 2021: 68 · 2020: 58 · 2019: 9
- FWCI
- 23.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drugs (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- onasemnogene abeparvovec, Zolgensma, spinal muscular atrophy, gene therapy, adeno-associated virus vectors, SMN1, survival motor neuron protein, pediatric patients, regulatory approval, drug development milestones
- MeSH terms
- Dependovirus, Genetic Vectors, Humans, Infant, Infant, Newborn, Infusions, Intravenous, Motor Neurons, Muscular Atrophy, Spinal, Mutation, United States, United States Food and Drug Administration, Genetic Therapy, Drug Approval, SMN Complex Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
