{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:53:32Z","timestamp":1790830412582,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"23","funder":[{"DOI":"10.13039\/501100001348","name":"A*STAR","doi-asserted-by":"crossref","award":["SPF2012\/005"],"award-info":[{"award-number":["SPF2012\/005"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001348","name":"A*STAR","doi-asserted-by":"crossref","award":["1331AFG078"],"award-info":[{"award-number":["1331AFG078"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"crossref","award":["IND-TEVA (1349157)"],"award-info":[{"award-number":["IND-TEVA (1349157)"]}],"id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,7]]},"abstract":"<jats:p>Pridopidine is currently under clinical development for Huntington disease (HD), with on-going studies to better characterize its therapeutic benefit and mode of action. Pridopidine was administered either prior to the appearance of disease phenotypes or in advanced stages of disease in the YAC128 mouse model of HD. In the early treatment cohort, animals received 0, 10, or 30 mg\/kg pridopidine for a period of 10.5 months. In the late treatment cohort, animals were treated for 8 weeks with 0 mg\/kg or an escalating dose of pridopidine (10 to 30 mg\/kg over 3 weeks). Early treatment improved motor coordination and reduced anxiety- and depressive-like phenotypes in YAC128 mice, but it did not rescue striatal and corpus callosum atrophy. Late treatment, conversely, only improved depressive-like symptoms. RNA-seq analysis revealed that early pridopidine treatment reversed striatal transcriptional deficits, upregulating disease-specific genes that are known to be downregulated during HD, a finding that is experimentally confirmed herein. This suggests that pridopidine exerts beneficial effects at the transcriptional level. Taken together, our findings support continued clinical development of pridopidine for HD, particularly in the early stages of disease, and provide valuable insight into the potential therapeutic mode of action of pridopidine.<\/jats:p>","DOI":"10.1172\/jci.insight.95665","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T11:00:32Z","timestamp":1512558032000},"source":"Crossref","is-referenced-by-count":41,"title":["Early pridopidine treatment improves behavioral and transcriptional deficits in YAC128 Huntington disease mice"],"prefix":"10.1172","volume":"2","author":[{"given":"Marta","family":"Garcia-Miralles","sequence":"first","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Geva","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Amirah Binte Mohammad","family":"Yusof","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonjeong","family":"Cha","sequence":"additional","affiliation":[{"name":"Immuneering Corporation, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Kusko","sequence":"additional","affiliation":[{"name":"Immuneering Corporation, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang Juin","family":"Tan","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Xu","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Grossman","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aric","family":"Orbach","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."},{"name":"Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel."},{"name":"Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada."},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Pouladi","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore."},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2017,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70245-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0112-2"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2013.116","article-title":"Imbalance of p75(NTR)\/TrkB protein expression in Huntington\u2019s disease: implication for neuroprotective therapies","volume":"4","author":"Brito","year":"2013","journal-title":"Cell Death Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.01.003"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.01.019"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2013.00114","article-title":"Dopamine imbalance in Huntington\u2019s disease: a mechanism for the lack of behavioral flexibility","volume":"7","author":"Chen","year":"2013","journal-title":"Front Neurosci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1038-15.2016"},{"issue":"Pt A","key":"B8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nbd.2016.10.006","article-title":"The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease","volume":"97","author":"Ryskamp","year":"2017","journal-title":"Neurobiol Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.08.007"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3997-8"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.09.007"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.12.043"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22534"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22274"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001680"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/156720511797633232"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2013.170","article-title":"Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-\u03baB pathway","volume":"4","author":"Hyrskyluoto","year":"2013","journal-title":"Cell Death Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12604"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.06.026"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.01.002"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1038\/srep31652","article-title":"Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of Huntington disease","volume":"6","author":"Garcia-Miralles","year":"2016","journal-title":"Sci Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3570"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds037"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0590-05.2005"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"issue":"Pt 4","key":"B27","first-page":"919","article-title":"Prevention of depressive behaviour in the YAC128 mouse model of Huntington disease by mutation at residue 586 of huntingtin","volume":"132","author":"Pouladi","year":"2009","journal-title":"Brain"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.03.018"},{"issue":"13","key":"B29","first-page":"2621","article-title":"Structural and molecular myelination deficits occur prior to neuronal loss in the YAC128 and BACHD models of Huntington disease","volume":"25","author":"Teo","year":"2016","journal-title":"Hum Mol Genet"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm133"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq018"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bau012","article-title":"COMPARTMENTS: unification and visualization of protein subcellular localization evidence","volume":"2014","author":"Binder","year":"2014","journal-title":"Database (Oxford)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4488-13.2014"},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2013.00042","article-title":"Expression of genes encoding the calcium signalosome in cellular and transgenic models of Huntington\u2019s disease","volume":"6","author":"Czeredys","year":"2013","journal-title":"Front Mol Neurosci"},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2199-9-84","article-title":"Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington\u2019s disease","volume":"9","author":"van Roon-Mom","year":"2008","journal-title":"BMC Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.05.003"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.02.008"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008201"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3246"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.03.003"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.102905"},{"key":"B43"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.07.001"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw238"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.CRJ04005X"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8974-4"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.07.023"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.2174\/187152710793361496"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_15"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.11.005"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.05.014"},{"issue":"Pt 7","key":"B53","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1093\/brain\/awu107","article-title":"Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism","volume":"137","author":"Francardo","year":"2014","journal-title":"Brain"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212049200"},{"issue":"5","key":"B55","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1471-4159.2010.06672.x","article-title":"Differential vulnerability of neurons in Huntington\u2019s disease: the role of cell type-specific features","volume":"113","author":"Han","year":"2010","journal-title":"J Neurochem"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv248"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417231112"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.019"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4965-11.2013"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31825fe154"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.07.008"},{"key":"B62","unstructured":"Gng4: G Protein Subunit Gamma 4. GeneCards: Human Gene Database. http:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=GNG4 Accessed November 9, 2017"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00441-1"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2652"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/0149-7634(85)90030-2"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.44"},{"issue":"115","key":"B67","doi-asserted-by":"crossref","DOI":"10.3791\/54348","article-title":"Determining immune system suppression versus CNS protection for pharmacological interventions in autoimmune demyelination","author":"Evonuk","year":"2016","journal-title":"J Vis Exp"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.1037"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/95665\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:16:52Z","timestamp":1779196612000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/95665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,7]]},"references-count":73,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2017,12,7]]},"published-print":{"date-parts":[[2017,12,7]]}},"alternative-id":["10.1172\/jci.insight.95665"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.95665","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,7]]},"article-number":"e95665"}}