Antisense oligonucleotide therapy for spinocerebellar ataxia type 2
Open accessAbstract
There are no disease-modifying treatments for adult human neurodegenerative diseases. Here we test RNA-targeted therapies in two mouse models of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine disease. Both models recreate the progressive adult-onset dysfunction and degeneration of a neuronal network that are seen in patients, including decreased firing frequency of cerebellar Purkinje cells and a decline in motor function. We developed a potential therapy directed at the ATXN2 gene by screening 152 antisense oligonucleotides (ASOs). The most promising oligonucleotide, ASO7, downregulated ATXN2 mRNA and protein, which resulted in delayed onset of the SCA2 phenotype. After delivery by intracerebroventricular injection to ATXN2-Q127 mice, ASO7 localized to Purkinje cells, reduced cerebellar ATXN2 expression below 75% for more than 10 weeks without microglial activation, and reduced the levels of cerebellar ATXN2. Treatment of symptomatic mice with ASO7 improved motor function compared to saline-treated mice. ASO7 had a similar effect in the BAC-Q72 SCA2 mouse model, and in both mouse models it normalized protein levels of several SCA2-related proteins expressed in Purkinje cells, including Rgs8, Pcp2, Pcp4, Homer3, Cep76 and Fam107b. Notably, the firing frequency of Purkinje cells returned to normal even when treatment was initiated more than 12 weeks after the onset of the motor phenotype in BAC-Q72 mice. These findings support ASOs as a promising approach for treating some human neurodegenerative diseases.
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ASOs can specifically alter levels and/or processing of a variety of proteins involved in neurodegenerative diseases, most of which have been the disease-causing protein itself.
“Due to the precision afforded by complementary binding of an ASO to its target transcript of interest, ASOs have emerged as an invaluable tool in specifically altering levels and/or processing of a variety of proteins involved in neurodegenerative diseases, most of which have been the disease-causing protein itself (38, 51–54).”
From Reduction of nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43–related neurodegeneration (2023) · cites this paper as [54]
The paper reports that sequence-specific ASO7 lowered the disease-causing ATXN2 protein in SCA2 models and discusses ASO approaches for other neurodegenerative diseases. It does not establish that most ASO targets across those diseases are the disease-causing proteins, or document altered protein processing. The supplied passages are labeled Abstract and have no page numbers. (LLM, conf=0.83)
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Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia
Xia, H., Mao, Q.-W., Eliason, S., Harper, S., Martins, I. H., Orr, H., Paulson, H., Yang, L., Kotin, R., & Davidson, B. (2004) · Nature Medicine · doi:10.1038/nm1076 · Cited by 689 · see citing works
Miller, T. M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S. H., Andres, P. L., Mahoney, K., Allred, P., Alexander, K., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70061-9 · Cited by 617 · see citing works
Self-citationTherapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice
Becker, L. A., Huang, B., Bieri, G., Ma, R., Knowles, D. A., Jafar-Nejad, P., Messing, J., Kim, H. J., Soriano, A., Auburger, G., et al. (2017) · Nature · doi:10.1038/nature22038 · Cited by 571 · see citing works
Self-citationSwayze, E. E., Siwkowski, A. M., Wancewicz, E. V., Migawa, M. T., Wyrzykiewicz, T. K., Hung, G., Monia, B. P., & Bennett, A. C. F. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl1071 · Cited by 473 · see citing works
Self-citationHuynh, D. P., Figueroa, K. P., Hoang, N., & Pulst, S.-M. (2000) · Nature Genetics · doi:10.1038/79162 · Cited by 330 · see citing works
Self-citationThe genetics and neuropathology of Parkinson’s disease
Houlden, H., & Singleton, A. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1013-5 · Cited by 320 · see citing works
Deranged Calcium Signaling and Neurodegeneration in Spinocerebellar Ataxia Type 2
Liu, J., Tang, T.-S., Tu, H., Nelson, O. L., Herndon, E., Huynh, D. P., Pulst, S. M., & Борисович, Б. И. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0660-09.2009 · Cited by 299 · see citing works
Self-citationCarroll, J. B., Warby, S. C., Southwell, A. L., Doty, C. N., Greenlee, S., Skotte, N. H., Hung, G., Bennett, C. F., Freier, S. M., & Hayden, M. R. (2011) · Molecular Therapy · doi:10.1038/mt.2011.201 · Cited by 294 · see citing works
Self-citationHansen, S. T., Meera, P., Otis, T. S., & Pulst, S. M. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds427 · Cited by 176 · see citing works
Self-citationMolecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABAA receptors
Meera, P., Wallner, M., & Otis, T. S. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00450.2011 · Cited by 161 · see citing works
Self-citationCircuit Mechanisms Underlying Motor Memory Formation in the Cerebellum
Lee, K. H., Mathews, P. J., Reeves, A. M. B., Choe, K. Y., Jami, S. A., Serrano, R. E., & Otis, T. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.010 · Cited by 145 · see citing works
Self-citationRGS4 Inhibits Signaling by Group I Metabotropic Glutamate Receptors
Saugstad, J. A., Marino, M. J., Folk, J. A., Hepler, J. R., & Conn, P. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-03-00905.1998 · Cited by 143 · see citing works
Skotte, N. H., Southwell, A. L., Østergaard, M. E., Carroll, J. B., Warby, S. C., Doty, C. N., Petoukhov, E., Vaid, K., Kordasiewicz, H. B., Watt, A. T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107434 · Cited by 116 · see citing works
Self-citationThe Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper
Lang, E. J., Apps, R., Bengtsson, F., Cerminara, N. L., Zeeuw, C. I. D., Ebner, T. J., Heck, D. H., Jaeger, D., Jörntell, H., Kawato, M., et al. (2016) · The Cerebellum · doi:10.1007/s12311-016-0787-8 · Cited by 114 · see citing works
Self-citationIngram, M. A. C., Wozniak, E. A. L., Duvick, L. A., Yang, R., Bergmann, P. E., Carson, R., O’Callaghan, B. L., Zoghbi, H. Y., Henzler, C. M., & Orr, H. T. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.011 · Cited by 104 · see citing works
Abdul‐Ghani, M. A., Valiante, T. A., Carlen, P. L., & Pennefather, P. (1996) · Journal of Neurophysiology · doi:10.1152/jn.1996.76.4.2691 · Cited by 99 · see citing works
Ataxin-2 Regulates RGS8 Translation in a New BAC-SCA2 Transgenic Mouse Model
Dansithong, W., Paul, S., Figueroa, K. P., Rinehart, M. D., Wiest, S., Pflieger, L. T., Scoles, D. R., & Pulst, S. M. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005182 · Cited by 95 · see citing works
Self-citationKeiser, M. S., Boudreau, R., & Davidson, B. (2014) · Molecular Therapy · doi:10.1038/mt.2013.279 · Cited by 81 · see citing works
Cellular and circuit mechanisms underlying spinocerebellar ataxias
Meera, P., Pulst, S. M., & Otis, T. S. (2016) · The Journal of Physiology · doi:10.1113/jp271897 · Cited by 79 · see citing works
Self-citationAnticipation in spinocerebellar ataxia type 2
Pulst, S.-M., Nechiporuk, A. V., & Starkman, S. (1993) · Nature Genetics · doi:10.1038/ng0993-8c · Cited by 77 · see citing works
Self-citationFittschen, M., Lastres‐Becker, I., Halbach, M. V., Damrath, E., Gispert, S., Azizov, M., Walter, M. J., Müller, S., & Auburger, G. W. J. (2015) · Neurogenetics · doi:10.1007/s10048-015-0441-5 · Cited by 72 · see citing works
Antisense Oligonucleotide-Based Therapies for Diseases Caused by pre-mRNA Processing Defects
Rigo, F., Seth, P. P., & Bennett, C. F. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-1221-6_9 · Cited by 71 · see citing works
Self-citationImpaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice
Peng, W., Blundon, J. A., Rong, Y., Zakharenko, S. S., & Morgan, J. I. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05208-11 · Cited by 68 · see citing works
Mizutani, A., Kuroda, Y., Futatsugi, A., Furuichi, T., & Mikoshiba, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4738-07.2008 · Cited by 65 · see citing works
Cep76, a Centrosomal Protein that Specifically Restrains Centriole Reduplication
Tsang, W. Y., Spektor, A., Vijayakumar, S., Bista, B. R., Li, J., Sánchez, I., Duensing, S. M., & Dynlacht, B. D. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.03.004 · Cited by 62 · see citing works
Dissociated Fear and Spatial Learning in Mice with Deficiency of Ataxin-2
Huynh, D. P., Maalouf, M., Silva, A. J., Schweizer, F. E., & Pulst, S. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006235 · Cited by 57 · see citing works
Self-citationAltered Purkinje cell miRNA expression and SCA1 pathogenesis
Rodríguez-Lebrón, E., Liu, G., Keiser, M. S., Behlke, M. A., & Davidson, B. L. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.01.019 · Cited by 42 · see citing works
Scoles, D. R., Ho, M. H. T., Dansithong, W., Pflieger, L. T., Petersen, L. W., Thai, K. K., & Pulst, S. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128769 · Cited by 41 · see citing works
Self-citationDegenerative ataxias, from genes to therapies
Pulst, S. M. (2016) · Neurology · doi:10.1212/wnl.0000000000002777 · Cited by 27 · see citing works
Self-citationIscru, E., Serinagaoglu, Y., Schilling, K., Tian, J., Bowers-Kidder, S. L., Zhang, R., Morgan, J. I., DeVries, A. C., Nelson, R. J., Zhu, M. X., et al. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.09.002 · Cited by 25 · see citing works
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- [29]Dansithong W Ataxin-2 regulates RGS8 translation in a new BAC-SCA2 transgenic mouse model. PLoS Genet 11, e1005182, doi: 10.1371/journal.pgen.1005182 (2015). 25902068 PMC4406435 · DOI
- [30]Hansen ST, Meera P, Otis TS & Pulst SM Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2. Hum Mol Genet 22, 271– 283, doi: 10.1093/hmg/dds427 (2013). 23087021 PMC3526159 · DOI
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Chen, W., Ouyang, J., Yi, X., Xu, Y., Niu, C., Zhang, W., Wang, L., Sheng, J., Deng, L., Liu, Y., et al. (2018) · Advanced Materials · doi:10.1002/adma.201703458 · Cited by 374 · see citing works
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Antisense Oligonucleotide Therapies for Neurodegenerative Diseases
Bennett, C. F., Krainer, A. R., & Cleveland, D. W. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050501 · Cited by 353 · see citing works
Self-citationAntisense oligonucleotides: translation from mouse models to human neurodegenerative diseases
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“ASO-mediated ATNX2 reduction in two separate SCA mouse models improvedmotor performance, corrected abnormal gene expression, and restored normal Purkinje cell electrophysiology (Scoles et al., 2017).”
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Nussbacher, J. K., Tabet, R., Yeo, G. W.-M., & Lagier‐Tourenne, C. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.014 · Cited by 264 · see citing works
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Ashizawa, T., Öz, G., & Paulson, H. L. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0051-6 · Cited by 251 · see citing works
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Hou, J., Wang, H., Ge, Z., Zuo, T., Chen, Q., Liu, X., Mou, S., Fan, C., Xie, Y., & Wang, L. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b05218 · Cited by 206 · see citing works
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Ye, X., Zhu, M., Che, X., Wang, H., Liang, X., Wu, C., Xue, X., & Yang, J. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1644-8 · Cited by 184 · see citing works
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Self-citationAntisense oligonucleotides extend survival of prion-infected mice
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Liu, Y., He, M., Yuan, Y., Nie, C., Wei, K., Zhang, T., Chen, T., & Chu, X. (2023) · ACS Nano · doi:10.1021/acsnano.3c00288 · Cited by 142 · see citing works
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Buijsen, R. A. M., Toonen, L. J. A., Gardiner, S. L., & van Roon‐Mom, W. (2019) · Neurotherapeutics · doi:10.1007/s13311-018-00696-y · Cited by 136 · see citing works
Bakthavachalu, B., Huelsmeier, J., Sudhakaran, I. P., Hillebrand, J., Singh, A., Petrauskas, A., Thiagarajan, D., Sankaranarayanan, M., Mizoue, L. S., Anderson, E. N., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.04.032 · Cited by 121 · see citing works
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Friedrich, J., Kordasiewicz, H. B., O’Callaghan, B., Handler, H. P., Wagener, C., Duvick, L., Swayze, E. E., Rainwater, O., Hofstra, B., Benneyworth, M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.123193 · Cited by 121 · see citing works
McMillan, M., Gomez, N., Hsieh, C., Bekier, M., Li, X., Miguez, R., Tank, E. M. H., & Barmada, S. J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.019 · Cited by 112 · see citing works
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Niu, C., Prakash, T. P., Kim, A., Quach, J., Huryn, L. A., Yang, Y., Lopez, E., Jazayeri, A., Hung, G., Sopher, B. L., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aap8677 · Cited by 89 · see citing works
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Bunting, E. L., Hamilton, J., & Tabrizi, S. J. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.07.001 · Cited by 88 · see citing works
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Oligonucleotide therapeutics in neurodegenerative diseases
Scoles, D. R., & Pulst, S. M. (2018) · RNA Biology · doi:10.1080/15476286.2018.1454812 · Cited by 72 · see citing works
Self-citationSilva, A. C., Lobo, D. D., Martins, I. M., Lopes, S., Henriques, C., Duarte, S., Dodart, J., Nobre, R. J., & de Almeida, L. P. (2019) · Brain · doi:10.1093/brain/awz328 · Cited by 72 · see citing works
Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases
Takeuchi, T., & Nagai, Y. (2017) · Brain Sciences · doi:10.3390/brainsci7100128 · Cited by 71 · see citing works
Ion channel dysfunction in cerebellar ataxia
Bushart, D. D., & Shakkottai, V. G. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.02.005 · Cited by 71 · see citing works
Spinocerebellar ataxia clinical trials: opportunities and challenges
Brooker, S. M., Edamakanti, C. R., Akasha, S. M., Kuo, S., & Opal, P. (2021) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51370 · Cited by 69 · see citing works
Pornnoppadol, G., Bond, L. G., Lucas, M. J., Zupancic, J. M., Kuo, Y., Zhang, B., Greineder, C. F., & Tessier, P. M. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.09.008 · Cited by 69 · see citing works
Díaz, J. C. R., Velázquez‐Pérez, L., Rodríguez‐Labrada, R., Rodríguez, R. A., Pérez, D. L., Ochoa, N. C., Montero, J. M., Estupiñán‐Rodríguez, A., Borjas, M. O., Marrero, M. G., et al. (2018) · Movement Disorders · doi:10.1002/mds.27437 · Cited by 68 · see citing works
Wilke, C., Bender, F., Hayer, S. N., Brockmann, K., Schöls, L. J., Kühle, J., & Synofzik, M. (2018) · Journal of Neurology · doi:10.1007/s00415-018-8893-9 · Cited by 68 · see citing works
Coarelli, G., Darios, F. D., Petit, E., Dorgham, K., Adanyeguh, I. M., Petit, E., Brice, A., Mochel, F., & Dürr, A. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105311 · Cited by 67 · see citing works
Auburger, G. W. J., Şen, N.-E., Meierhofer, D., Başak, A. N., & Gitler, A. D. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.06.004 · Cited by 67 · see citing works
Molecular landscape of long noncoding RNAs in brain disorders
Yang, S., Lim, K., Kim, S.-H., & Joo, J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00947-5 · Cited by 66 · see citing works
Hagedorn, P., Brown, J. M., Easton, A. E., Pierdomenico, M., Jones, K. M., Olson, R. E., Mercer, S. E., Li, D., Loy, J. K., Høg, A. M., et al. (2022) · Nucleic Acid Therapeutics · doi:10.1089/nat.2021.0071 · Cited by 64 · see citing works
Systematic evaluation of genetic mutations in ALS: a population-based study
Grassano, M., Calvo, A., Moglia, C., Sbaiz, L., Brunetti, M., Barberis, M., Casale, F., Manera, U., Vasta, R., Canosa, A., et al. (2022) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-328931 · Cited by 66 · see citing works
Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2
Reetz, K., Rodríguez‐Labrada, R., Dogan, I., Mirzazade, S., Romanzetti, S., Schulz, J. B., Cruz-Rivas, E., Álvarez-Cuesta, J. A., Rodríguez, R. A., Zaldívar, Y. G., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.504 · Cited by 65 · see citing works
MSGP: the first database of the protein components of the mammalian stress granules
Nunes, C., Mestre, I., Marcelo, A., Koppenol, R., Matos, C. A., & Nóbrega, C. (2019) · Database · doi:10.1093/database/baz031 · Cited by 65 · see citing works
Antisense oligonucleotide therapy in a humanized mouse model of MECP2 duplication syndrome
Shao, Y., Sztainberg, Y., Wang, Q., Bajikar, S. S., Trostle, A. J., Wan, Y., Jafar‐Nejad, P., Rigo, F., Liu, Z., Tang, J., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz7785 · Cited by 61 · see citing works
Self-citationCurrent and emerging treatment modalities for spinocerebellar ataxias
Ghanekar, S. D., Kuo, S., Staffetti, J. S., & Zesiewicz, T. A. (2022) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2022.2029703 · Cited by 61 · see citing works
Exploring the Role of Ubiquitin–Proteasome System in Parkinson's Disease
Behl, T., Kumar, S., Althafar, Z. M., Sehgal, A., Singh, S., Sharma, N., Badavath, V. N., Yadav, S., Bhatia, S., Al‐Harrasi, A., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02851-1 · Cited by 61 · see citing works
Advances on Therapeutic Strategies for Alzheimer’s Disease: From Medicinal Plant to Nanotechnology
Hassan, N. A., Alshamari, A. K., Hassan, A. A., Elharrif, M. G., Alhajri, A. M., Sattam, M., & Khattab, R. R. (2022) · Molecules · doi:10.3390/molecules27154839 · Cited by 61 · see citing works
Alqinyah, M., & Hooks, S. B. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.10.007 · Cited by 59 · see citing works
RNA dysregulation in neurodegenerative diseases
Li, Y., & Sun, S. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00352-6 · Cited by 62 · see citing works
Coarelli, G., Heinzmann, A., Ewenczyk, C., Fischer, C., Marie Chupin, A., Monin, M., Hurmic, H., Calvas, F., Calvas, P., Goizet, C., et al. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00457-9 · Cited by 58 · see citing works
Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2
Egorova, P. A., & Борисович, Б. И. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00777-6 · Cited by 57 · see citing works
Kuo, S. (2019) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000753 · Cited by 55 · see citing works
Figueroa, K. P., Groß, C., Buena‐Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01719-5 · Cited by 55 · see citing works
Self-citationCanet-Pons, J., Şen, N.-E., Arsović, A., Almaguer-Mederos, L. E., Halbach, M. V., Key, J., Döring, C., Kerksiek, A., Picchiarelli, G., Cassel, R., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105289 · Cited by 54 · see citing works
A single-cell map of antisense oligonucleotide activity in the brain
Mortberg, M. A., Gentile, J. E., Nadaf, N. M., Vanderburg, C., Simmons, S., Dubinsky, D., Slamin, A., Maldonado, S., Petersen, C. L., Jones, N., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad371 · Cited by 54 · see citing works
Gene suppression approaches to neurodegeneration
Ghosh, R., & Tabrizi, S. J. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0307-1 · Cited by 55 · see citing works
SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function
Bae, M. H., Roh, J. D., Kim, Y.-J., Kim, S. S., Han, H. M., Yang, E., Kang, H., Lee, S., Kim, J. Y., Kang, R., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202012632 · Cited by 52 · see citing works
Coarelli, G., Brice, A., & Dürr, A. (2018) · F1000Research · doi:10.12688/f1000research.15788.1 · Cited by 52 · see citing works
Pflieger, L. T., Dansithong, W., Paul, S., Scoles, D. R., Figueroa, K. P., Meera, P., Otis, T. S., Facelli, J. C., & Pulst, S. M. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx191 · Cited by 51 · see citing works
Self-citationDing, T., Cui, P., Zhou, Y., Chen, C., Zhao, J., Wang, H., Guo, M., He, Z., & Xu, L. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.09.004 · Cited by 50 · see citing works
Protein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases
Minakawa, E. N., & Nagai, Y. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.621996 · Cited by 50 · see citing works
He, L., Wang, S., Peng, L., Zhao, H., Li, S., Han, X. B., Habimana, J. D. D., Chen, Z., Wang, C., Peng, Y., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01605-2 · Cited by 49 · see citing works
Wang, J., Xu, L., Lin, W., Yao, Y., Li, H., Shen, G., Cao, X., He, N., Chen, J., Hu, J., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04864-z · Cited by 50 · see citing works
Long-term RNAi knockdown of α-synuclein in the adult rat substantia nigra without neurodegeneration
Zharikov, A., Bai, Q., Miranda, B. R. D., Laar, A. D. V., Greenamyre, J. T., & Burton, E. A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.01.004 · Cited by 48 · see citing works
An RNA/DNA hybrid origami-based nanoplatform for efficient gene therapy
Wu, X., Liu, Q. L., Liu, F., Wu, T., Shang, Y., Liu, J., & Ding, B. (2021) · Nanoscale · doi:10.1039/d1nr00517k · Cited by 49 · see citing works
Paving the Way Toward Meaningful Trials in Ataxias: An Ataxia Global Initiative Perspective
Klockgether, T., Ashizawa, T., Brais, B., Chuang, R., Dürr, A., Fogel, B. L., Greenfield, J., Hagen, S., Jardim, L. B., Jiang, H. F., et al. (2022) · Movement Disorders · doi:10.1002/mds.29032 · Cited by 47 · see citing works
Mohan, A., Fitzsimmons, B., Zhao, H. T., Jiang, Y., Mazur, C., Swayze, E. E., & Kordasiewicz, H. B. (2017) · Pain · doi:10.1097/j.pain.0000000000001074 · Cited by 46 · see citing works
Ferro, A., Sheeler, C. A., Rosa, J. S., & Cvetanović, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.016 · Cited by 46 · see citing works
Role and therapeutic potential of liquid–liquid phase separation in amyotrophic lateral sclerosis
Pakravan, D., Orlando, G., Bercier, V., & Bosch, L. V. D. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa049 · Cited by 46 · see citing works
Şen, N.-E., Canet-Pons, J., Halbach, M. V., Arsović, A., Pilatus, U., Chae, W. H., Güleç, Z. E. K., Seidel, K., Rollmann, E., Mittelbronn, M. G. A., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104559 · Cited by 44 · see citing works
Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade
Cantara, S., Simoncelli, G., & Ricci, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094809 · Cited by 43 · see citing works
Clayton, E. L., Milioto, C., Muralidharan, B., Norona, F. E., Edgar, J. R., Soriano, A., Jafar‐Nejad, P., Rigo, F., Collinge, J., & Isaacs, A. M. (2018) · Brain · doi:10.1093/brain/awy284 · Cited by 44 · see citing works
Self-citationThe polyglutamine protein ATXN2: from its molecular functions to its involvement in disease
da Costa, R. G., Conceição, A., Matos, C. A., & Nóbrega, C. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06812-5 · Cited by 42 · see citing works
Deep cerebellar stimulation reduces ataxic motor symptoms in the shaker rat
Anderson, C. J., Figueroa, K. P., Dorval, A. D., & Pulst, S. M. (2019) · Annals of Neurology · doi:10.1002/ana.25464 · Cited by 42 · see citing works
Self-citationPathogenic mechanisms underlying spinocerebellar ataxia type 1
Tejwani, L., & Lim, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03520-z · Cited by 38 · see citing works
Chang, Z., Chen, Z., Stephen, C. D., Schmahmann, J. D., Wu, H., Sapiro, G., & Gupta, A. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-75661-x · Cited by 42 · see citing works
Epidemiology of inherited cerebellar ataxias and challenges in clinical research
Pilotto, F., & Saxena, S. (2018) · Clinical and Translational Neuroscience · doi:10.1177/2514183x18785258 · Cited by 41 · see citing works
Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins
C., M. A. Z., Moore, H. J., Smith, T. J. S., Powell, J. E., Ahsan, N. S., Zhang, S., & Gaj, T. (2023) · Nature Communications · doi:10.1038/s41467-023-42147-z · Cited by 41 · see citing works
Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development
Zhong, S., Wang, M., Huang, L., Chen, Y., Ge, Y., Zhang, J., Shi, Y., Dong, H., Zhou, X., Wang, B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43568-6 · Cited by 41 · see citing works
- Authors
- Scoles, D. R., Meera, P., Schneider, M. D., Paul, S., Dansithong, W., Figueroa, K. P., Hung, G., Rigo, F., Bennett, C. F., Otis, T. S., & Pulst, S. M.
- Affiliations
- University of Utah (US)
- University of California, Los Angeles (US)
- Ionis Pharmaceuticals (United States) (US)
- Corresponding author
- Scoles, Daniel R.
- Pulst, Stefan M.
- ORCID
- Venue
- Nature
- Published
- 2017-04-12
- Volume
- 544
- Issue
- 7650
- Pages
- 362-366
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6625650
- OpenAlex
- W2606911774
- Cited by
- 319
- References
- 31
- Citations by year
- 2026: 17 · 2025: 24 · 2024: 26 · 2023: 28 · 2022: 39 · 2021: 37 · 2020: 37 · 2019: 43 · 2018: 45 · 2017: 21 · 2012: 1
- FWCI
- 19.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Target ALS
- National Institute of Neurological Disorders and Stroke (U01NS103883, R01NS033123, R01NS090930, R21NS081182, RC4NS073009, R56NS033123, R01NS097903, R37NS033123, R21NS103009)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- spinocerebellar ataxia type 2, antisense oligonucleotides, ATXN2, polyglutamine expansion, Purkinje cells, TDP-43 aggregation, amyotrophic lateral sclerosis, RNA-targeted therapeutics, neurodegeneration, mouse model, motor function, lifespan
- MeSH terms
- Ataxin-2, Action Potentials, Animals, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Male, Mice, Transgenic, Movement, Phenotype, Purkinje Cells, RNA, Messenger, Oligonucleotides, Antisense, Spinocerebellar Ataxias, Rotarod Performance Test, Mice
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