{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:51:54Z","timestamp":1789487514192,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805200"],"award-info":[{"award-number":["2021YFA0805200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Preclinical studies have suggested that DL\u20103\u2010\n                      <jats:italic>n<\/jats:italic>\n                      \u2010butylphthalide (NBP) may exhibit neuroprotective effects in neurodegenerative diseases; however, no human trial has evaluated NBP in spinocerebellar ataxia type 3 (SCA3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim of the study was to evaluate the efficacy and safety of oral NBP in patients with SCA3 over 12\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were randomly assigned (1:1) to oral NBP (200\u2009mg thrice daily) or placebo for 12\u2009months. The primary outcomes were 12\u2010month changes in the Scale for Assessment and Rating of Ataxia (SARA) and Spinocerebellar Ataxia Functional Index (SCAFI). Safety outcomes included adverse events (AEs) and serious adverse events (SAEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The modified intention\u2010to\u2010treat (mITT) population included 116 patients (NBP, n\u2009=\u200956; placebo, n\u2009=\u200960). The primary endpoints, change in SARA and SCAFI, were significantly different between NBP and placebo groups (SARA, estimated marginal mean difference: \u22120.86, 95% confidence interval [CI]: \u22121.56 to \u22120.16,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02; SCAFI, estimated marginal mean difference: 0.16, 95% CI: 0.01\u20130.31,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03) in mITT population using a mixed\u2010effect model, with improved clinical outcome in the NBP group. Overall, AE rates were not significantly different between groups (13 AEs [23.2%] in NBP vs. 9 AEs [15%] in placebo,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.26), although drug\u2010related AEs were numerically more frequent with NBP (12 [21.4%] vs. 6 [10.0%],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.09); no SAE occurred in either group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral administration of NBP was safe and generally well tolerated. Significant differences in clinical outcomes were observed in the treatment group compared to the placebo. NBP administration showed preliminary evidence of clinical benefit in SCA3. \u00a9 2026 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70499","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:43:06Z","timestamp":1789483386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of\n                    <scp>DL<\/scp>\n                    \u20103\u2010\n                    <i>n<\/i>\n                    \u2010Butylphthalide in Spinocerebellar Ataxia Type 3"],"prefix":"10.1002","author":[{"given":"Xiaokai","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3750-7935","authenticated-orcid":false,"given":"Jingyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"},{"name":"Department of Radiology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Medical Research Center for Stroke Prevention and Treatment of Hunan Province, Department of Neurology, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-3454","authenticated-orcid":false,"given":"Yun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"},{"name":"Department of Pathology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"},{"name":"Department of Radiology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linliu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-1576","authenticated-orcid":false,"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Radiology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Burrell","sequence":"additional","affiliation":[{"name":"Neurology Department, Macquarie University Health Macquarie University  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital, Central South University  Changsha China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-4120","authenticated-orcid":false,"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital, Central South University  Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital, Central South University  Changsha China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases  Changsha China"},{"name":"Department of Neurology, The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-019-0074-3","article-title":"Spinocerebellar ataxia","volume":"5","author":"Klockgether T","year":"2019","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41582-018-0051-6","article-title":"Spinocerebellar ataxias: prospects and challenges for therapy development","volume":"14","author":"Ashizawa T","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"e_1_2_9_4_1","first-page":"143","volume-title":"Handbook of Clinical Neurology","author":"Soong BW","year":"2018"},{"issue":"2","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00415-018-9076-4","article-title":"Spinocerebellar ataxia: an update","volume":"266","author":"Sullivan R","year":"2019","journal-title":"J Neurol"},{"issue":"3","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000358801","article-title":"The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies","volume":"42","author":"Ruano L","year":"2014","journal-title":"Neuroepidemiology"},{"issue":"2","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/brain\/awu352","article-title":"Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado\u2010Joseph disease mice","volume":"138","author":"Mendon\u00e7a LS","year":"2015","journal-title":"Brain"},{"issue":"9","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/j.ymthe.2018.07.007","article-title":"Repeated mesenchymal stromal cell treatment sustainably alleviates Machado\u2010Joseph disease","volume":"26","author":"Oliveira Miranda C","year":"2018","journal-title":"Mol Ther"},{"issue":"10","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1212\/WNL.0000000000005055","article-title":"Comprehensive systematic review summary: treatment of cerebellar motor dysfunction and ataxia: report of the guideline development, dissemination, and implementation Subcommittee of the American Academy of neurology","volume":"90","author":"Zesiewicz TA","year":"2018","journal-title":"Neurology"},{"issue":"2","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jalz.2015.04.010","article-title":"The effects of DL\u20103\u2010n\u2010butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: a multicentre, randomized, double\u2010blind, placebo\u2010controlled trial","volume":"12","author":"Jia J","year":"2016","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/5012341","article-title":"A review of recent advances in neuroprotective potential of 3\u2010N\u2010butylphthalide and its derivatives","volume":"2016","author":"Abdoulaye IA","year":"2016","journal-title":"Biomed Res Int"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.phrs.2018.08.007","article-title":"From stroke to neurodegenerative diseases: the multi\u2010target neuroprotective effects of 3\u2010n\u2010butylphthalide and its derivatives","volume":"135","author":"Huang L","year":"2018","journal-title":"Pharmacol Res"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.2147\/NDT.S179453","article-title":"The efficacy of a \u2018cocktail therapy\u2019 on Parkinson's disease with dementia","volume":"15","author":"Zhang C","year":"2019","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"2","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3233\/JAD-201381","article-title":"Donepezil combined with DL\u20103\u2010n\u2010butylphthalide delays cognitive decline in patients with mild to moderate Alzheimer's disease: a multicenter, prospective cohort study","volume":"80","author":"Wang J","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.neuropharm.2017.02.014","article-title":"n\u2010Butylidenephthalide exhibits protection against neurotoxicity through regulation of tryptophan 2, 3 dioxygenase in spinocerebellar ataxia type 3","volume":"117","author":"Rajamani K","year":"2017","journal-title":"Neuropharmacology"},{"issue":"12","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22126339","article-title":"n\u2010Butylidenephthalide modulates autophagy to ameliorate neuropathological Progress of spinocerebellar ataxia type 3 through mTOR pathway","volume":"22","author":"Lee JH","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"11","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: development of a new clinical scale","volume":"66","author":"Schmitz\u2010H\u00fcbsch T","year":"2006","journal-title":"Neurology"},{"issue":"7","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1212\/01.wnl.0000324863.76290.19","article-title":"SCA functional index: a useful compound performance measure for spinocerebellar ataxia","volume":"71","author":"Schmitz\u2010H\u00fcbsch T","year":"2008","journal-title":"Neurology"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2020.00749","article-title":"MR imaging of SCA3\/MJD","volume":"14","author":"Wan N","year":"2020","journal-title":"Front Neurosci"},{"issue":"1","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13024-019-0338-0","article-title":"Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3","volume":"14","author":"Li Q\u2010F","year":"2019","journal-title":"Mol Neurodegener"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2021.105311","article-title":"Plasma neurofilament light chain predicts cerebellar atrophy and clinical progression in spinocerebellar ataxia","volume":"153","author":"Coarelli G","year":"2021","journal-title":"Neurobiol Dis"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"T72","DOI":"10.1016\/j.neuroimage.2009.05.013","article-title":"Patterns of fractional anisotropy changes in white matter of cerebellar peduncles distinguish spinocerebellar ataxia\u20101 from multiple system atrophy and other ataxia syndromes","volume":"47","author":"Prakash N","year":"2009","journal-title":"Neuroimage"},{"issue":"3","key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/hbm.26113","article-title":"Cerebello\u2010cerebral resting\u2010state functional connectivity in spinocerebellar ataxia type 3","volume":"44","author":"Guo J","year":"2022","journal-title":"Hum Brain Mapp"},{"issue":"5","key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2174\/1871527317666180612125843","article-title":"Dl\u20103\u2010n\u2010butylphthalide (NBP): a promising therapeutic agent for ischemic stroke","volume":"17","author":"Wang S","year":"2018","journal-title":"CNS Neurol Disord Drug Targets"},{"issue":"3","key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1097\/CM9.0000000000002442","article-title":"A multicenter, randomized, double blind, placebo\u2010controlled clinical trial of DL\u20103\u2010n\u2010butylphthalide in treatment of amyotrophic lateral sclerosis","volume":"136","author":"Liu M","year":"2023","journal-title":"Chin Med J (Engl)"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70499","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70499","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:43:10Z","timestamp":1789483390000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":24,"alternative-id":["10.1002\/mds.70499"],"URL":"https:\/\/doi.org\/10.1002\/mds.70499","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"assertion":[{"value":"2025-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mds.70499"}}