{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:18:19Z","timestamp":1791919099093,"version":"4.3.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7650","license":[{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2017,4,20]]},"DOI":"10.1038\/nature22044","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T12:31:31Z","timestamp":1491913891000},"page":"362-366","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":336,"title":["Antisense oligonucleotide therapy for spinocerebellar ataxia type 2"],"prefix":"10.1038","volume":"544","author":[{"given":"Daniel R.","family":"Scoles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratap","family":"Meera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharan","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warunee","family":"Dansithong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla P.","family":"Figueroa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Frank","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Otis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Pulst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,12]]},"reference":[{"key":"BFnature22044_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/978-1-4939-1221-6_9","volume":"825","author":"F Rigo","year":"2014","unstructured":"Rigo, F., Seth, P. P. & Bennett, C. F. Antisense oligonucleotide-based therapies for diseases caused by pre-mRNA processing defects. Adv. Exp. Med. Biol. 825, 303\u2013352 (2014)","journal-title":"Adv. Exp. Med. Biol."},{"key":"BFnature22044_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/ng0993-8c","volume":"5","author":"SM Pulst","year":"1993","unstructured":"Pulst, S. M., Nechiporuk, A. & Starkman, S. Anticipation in spinocerebellar ataxia type 2. Nat. Genet. 5, 8\u201310 (1993)","journal-title":"Nat. Genet."},{"key":"BFnature22044_CR3","doi-asserted-by":"publisher","first-page":"e1005182","DOI":"10.1371\/journal.pgen.1005182","volume":"11","author":"W Dansithong","year":"2015","unstructured":"Dansithong, W. et al. Ataxin-2 regulates RGS8 translation in a new BAC-SCA2 transgenic mouse model. PLoS Genet. 11, e1005182 (2015)","journal-title":"PLoS Genet."},{"key":"BFnature22044_CR4","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1093\/hmg\/dds427","volume":"22","author":"ST Hansen","year":"2013","unstructured":"Hansen, S. T., Meera, P., Otis, T. S. & Pulst, S. M. Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2. Hum. Mol. Genet. 22, 271\u2013283 (2013)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature22044_CR5","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1212\/WNL.0000000000002777","volume":"86","author":"SM Pulst","year":"2016","unstructured":"Pulst, S. M. Degenerative ataxias, from genes to therapies: The 2015 Cotzias Lecture. Neurology 86, 2284\u20132290 (2016)","journal-title":"Neurology"},{"key":"BFnature22044_CR6","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00401-012-1013-5","volume":"124","author":"H Houlden","year":"2012","unstructured":"Houlden, H. & Singleton, A. B. The genetics and neuropathology of Parkinson\u2019s disease. Acta Neuropathol. 124, 325\u2013338 (2012)","journal-title":"Acta Neuropathol."},{"key":"BFnature22044_CR7","doi-asserted-by":"publisher","first-page":"e0128769","DOI":"10.1371\/journal.pone.0128769","volume":"10","author":"DR Scoles","year":"2015","unstructured":"Scoles, D. R. et al. Repeat associated non-AUG translation (RAN translation) dependent on sequence downstream of the ATXN2 CAG repeat. PLoS One 10, e0128769 (2015)","journal-title":"PLoS One"},{"key":"BFnature22044_CR8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/79162","volume":"26","author":"DP Huynh","year":"2000","unstructured":"Huynh, D. P., Figueroa, K., Hoang, N. & Pulst, S. M. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human. Nat. Genet. 26, 44\u201350 (2000)","journal-title":"Nat. Genet."},{"key":"BFnature22044_CR9","doi-asserted-by":"publisher","first-page":"e6235","DOI":"10.1371\/journal.pone.0006235","volume":"4","author":"DP Huynh","year":"2009","unstructured":"Huynh, D. P., Maalouf, M., Silva, A. J., Schweizer, F. E. & Pulst, S. M. Dissociated fear and spatial learning in mice with deficiency of ataxin-2. PLoS One 4, e6235 (2009)","journal-title":"PLoS One"},{"key":"BFnature22044_CR10","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1523\/JNEUROSCI.18-03-00905.1998","volume":"18","author":"JA Saugstad","year":"1998","unstructured":"Saugstad, J. A., Marino, M. J., Folk, J. A., Hepler, J. R. & Conn, P. J. RGS4 inhibits signaling by group I metabotropic glutamate receptors. J. Neurosci. 18, 905\u2013913 (1998)","journal-title":"J. Neurosci."},{"key":"BFnature22044_CR11","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1152\/jn.1996.76.4.2691","volume":"76","author":"MA Abdul-Ghani","year":"1996","unstructured":"Abdul-Ghani, M. A., Valiante, T. A., Carlen, P. L. & Pennefather, P. S. Metabotropic glutamate receptors coupled to IP3 production mediate inhibition of IAHP in rat dentate granule neurons. J. Neurophysiol. 76, 2691\u20132700 (1996)","journal-title":"J. Neurophysiol."},{"key":"BFnature22044_CR12","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1113\/JP271897","volume":"594","author":"P Meera","year":"2016","unstructured":"Meera, P., Pulst, S. M. & Otis, T. S. Cellular and circuit mechanisms underlying spinocerebellar ataxias. J. Physiol. (Lond.) 594, 4653\u20134660 (2016)","journal-title":"J. Physiol. (Lond.)"},{"key":"BFnature22044_CR13","doi-asserted-by":"publisher","first-page":"5369","DOI":"10.1523\/JNEUROSCI.4738-07.2008","volume":"28","author":"A Mizutani","year":"2008","unstructured":"Mizutani, A., Kuroda, Y., Futatsugi, A., Furuichi, T. & Mikoshiba, K. Phosphorylation of Homer3 by calcium\/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells. J. Neurosci. 28, 5369\u20135382 (2008)","journal-title":"J. Neurosci."},{"key":"BFnature22044_CR14","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.mcn.2008.09.002","volume":"40","author":"E Iscru","year":"2009","unstructured":"Iscru, E. et al. Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi\/o modulator, Pcp2(L7). Mol. Cell. Neurosci. 40, 62\u201375 (2009)","journal-title":"Mol. Cell. Neurosci."},{"key":"BFnature22044_CR15","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1128\/MCB.05208-11","volume":"31","author":"P Wei","year":"2011","unstructured":"Wei, P., Blundon, J. A., Rong, Y., Zakharenko, S. S. & Morgan, J. I. Impaired locomotor learning and altered cerebellar synaptic plasticity in pep-19\/PCP4-null mice. Mol. Cell. Biol. 31, 2838\u20132844 (2011)","journal-title":"Mol. Cell. Biol."},{"key":"BFnature22044_CR16","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.devcel.2009.03.004","volume":"16","author":"WY Tsang","year":"2009","unstructured":"Tsang, W. Y. et al. Cep76, a centrosomal protein that specifically restrains centriole reduplication. Dev. Cell 16, 649\u2013660 (2009)","journal-title":"Dev. Cell"},{"key":"BFnature22044_CR17","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.neuron.2016.02.011","volume":"89","author":"M Ingram","year":"2016","unstructured":"Ingram, M. et al. Cerebellar transcriptome profiles of ATXN1 transgenic mice reveal SCA1 disease progression and protection pathways. Neuron 89, 1194\u20131207 (2016)","journal-title":"Neuron"},{"key":"BFnature22044_CR18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10048-015-0441-5","volume":"16","author":"M Fittschen","year":"2015","unstructured":"Fittschen, M. et al. Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate. Neurogenetics 16, 181\u2013192 (2015)","journal-title":"Neurogenetics"},{"key":"BFnature22044_CR19","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.neuron.2015.03.010","volume":"86","author":"KH Lee","year":"2015","unstructured":"Lee, K. H. et al. Circuit mechanisms underlying motor memory formation in the cerebellum. Neuron 86, 529\u2013540 (2015)","journal-title":"Neuron"},{"key":"BFnature22044_CR20","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1007\/s12311-016-0787-8","volume":"16","author":"EJ Lang","year":"2017","unstructured":"Lang, E. J. et al. The roles of the olivocerebellar pathway in motor learning and motor control. A consensus paper. Cerebellum 16, 230\u2013252 (2017)","journal-title":"Cerebellum"},{"key":"BFnature22044_CR21","doi-asserted-by":"publisher","first-page":"9148","DOI":"10.1523\/JNEUROSCI.0660-09.2009","volume":"29","author":"J Liu","year":"2009","unstructured":"Liu, J. et al. Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2. J. Neurosci. 29, 9148\u20139162 (2009)","journal-title":"J. Neurosci."},{"key":"BFnature22044_CR22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S1474-4422(13)70061-9","volume":"12","author":"TM Miller","year":"2013","unstructured":"Miller, T. M. et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 12, 435\u2013442 (2013)","journal-title":"Lancet Neurol."},{"key":"BFnature22044_CR23","doi-asserted-by":"publisher","first-page":"e107434","DOI":"10.1371\/journal.pone.0107434","volume":"9","author":"NH Skotte","year":"2014","unstructured":"Skotte, N. H. et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One 9, e107434 (2014)","journal-title":"PLoS One"},{"key":"BFnature22044_CR24","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1038\/mt.2011.201","volume":"19","author":"JB Carroll","year":"2011","unstructured":"Carroll, J. B. et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene\/allele-specific silencing of mutant huntingtin. Mol. Ther. 19, 2178\u20132185 (2011)","journal-title":"Mol. Ther."},{"key":"BFnature22044_CR25","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/nm1076","volume":"10","author":"H Xia","year":"2004","unstructured":"Xia, H. et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 10, 816\u2013820 (2004)","journal-title":"Nat. Med."},{"key":"BFnature22044_CR26","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/mt.2013.279","volume":"22","author":"MS Keiser","year":"2014","unstructured":"Keiser, M. S., Boudreau, R. L. & Davidson, B. L. Broad therapeutic benefit after RNAi Expression vector delivery to deep cerebellar nuclei: implications for spinocerebellar ataxia type 1 therapy. Mol. Ther. 22, 588\u2013595 (2014)","journal-title":"Mol. Ther."},{"key":"BFnature22044_CR27","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.nbd.2013.01.019","volume":"54","author":"E Rodriguez-Lebron","year":"2013","unstructured":"Rodriguez-Lebron, E., Liu, G., Keiser, M., Behlke, M. A. & Davidson, B. L. Altered Purkinje cell miRNA expression and SCA1 pathogenesis. Neurobiol. Dis. 54, 456\u2013463 (2013)","journal-title":"Neurobiol. Dis."},{"key":"BFnature22044_CR28","doi-asserted-by":"publisher","unstructured":"Becker, L. A. et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature \n                    http:\/\/dx.doi.org\/10.1038\/nature22038\n                    \n                   (2017)","DOI":"10.1038\/nature22038"},{"key":"BFnature22044_CR29","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1093\/nar\/gkl1071","volume":"35","author":"EE Swayze","year":"2007","unstructured":"Swayze, E. E. et al. Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals. Nucleic Acids Res. 35, 687\u2013700 (2007)","journal-title":"Nucleic Acids Res."},{"key":"BFnature22044_CR30","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009)","journal-title":"Genome Biol."},{"key":"BFnature22044_CR31","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1152\/jn.00450.2011","volume":"106","author":"P Meera","year":"2011","unstructured":"Meera, P., Wallner, M. & Otis, T. S. Molecular basis for the high THIP\/gaboxadol sensitivity of extrasynaptic GABAA receptors. J. Neurophysiol. 106, 2057\u20132064 (2011)","journal-title":"J. Neurophysiol."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature22044.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature22044","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nature22044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nature22044.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:01:05Z","timestamp":1684418465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature22044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,12]]},"references-count":31,"journal-issue":{"issue":"7650","published-print":{"date-parts":[[2017,4,20]]}},"alternative-id":["BFnature22044"],"URL":"https:\/\/doi.org\/10.1038\/nature22044","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727503963.793552251","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,12]]},"assertion":[{"value":"24 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.M.P. is a consultant for Progenitor Life Sciences and Ataxion Pharmaceuticals. T.S.O. is an employee of F. Hoffmann-La Roche, Ltd. G.H., F.R. and C.F.B are employed by Ionis Pharmaceuticals, which supplied the ASOs used in the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}