{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"33285037"},"DateCompleted":{"Year":"2021","Month":"11","Day":"01"},"DateRevised":{"Year":"2022","Month":"10","Day":"05"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"2328-9503"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"7","Issue":"12","PubDate":{"Year":"2020","Month":"Dec"}},"Title":"Annals of clinical and translational neurology","ISOAbbreviation":"Ann Clin Transl Neurol"},"ArticleTitle":"Viltolarsen in Japanese Duchenne muscular dystrophy patients: A phase 1\/2 study.","Pagination":{"StartPage":"2393","EndPage":"2408","MedlinePgn":"2393-2408"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1002\/acn3.51235"}],"Abstract":{"AbstractText":[{"@attributes":{"Label":"OBJECTIVE"},"@text":"The novel morpholino antisense oligonucleotide viltolarsen targets exon 53 of the dystrophin gene, and could be an effective treatment for patients with Duchenne muscular dystrophy (DMD). We investigated viltolarsen's ability to induce dystrophin expression and examined its safety in DMD patients."},{"@attributes":{"Label":"METHODS"},"@text":"In this open-label, multicenter, parallel-group, phase 1\/2, exploratory study, 16 ambulant and nonambulant males aged 5-12\u00a0years with DMD received viltolarsen 40 or 80\u00a0mg\/kg\/week via intravenous infusion for 24\u00a0weeks. Primary endpoints were dystrophin expression and exon 53 skipping levels."},{"@attributes":{"Label":"RESULTS"},"@text":"In western blot analysis, mean changes in dystrophin expression (% normal) from baseline to Weeks 12 and 24 were\u00a0-\u00a01.21 (P\u00a0=\u00a00.5136) and 1.46 (P\u00a0=\u00a00.1636), respectively, in the 40\u00a0mg\/kg group, and 0.76 (P\u00a0=\u00a00.2367) and 4.81 (P\u00a0=\u00a00.0536), respectively, in the 80\u00a0mg\/kg group. The increase in mean dystrophin level at Weeks 12 and 24 was significant in the 80\u00a0mg\/kg group (2.78%; P\u00a0=\u00a00.0364). Patients receiving 80\u00a0mg\/kg showed a higher mean exon 53 skipping level (42.4%) than those receiving 40\u00a0mg\/kg (21.8%). All adverse events were judged to be mild or moderate in intensity and none led to study discontinuation."},{"@attributes":{"Label":"INTERPRETATION"},"@text":"Treatment with viltolarsen 40 or 80\u00a0mg\/kg elicited an increasing trend in dystrophin expression and exon 53 skipping levels, and was safe and well tolerated. The decline in motor function appeared less marked in patients with higher dystrophin levels; this may warrant further investigation. This study supports the potential clinical benefit of viltolarsen."}],"CopyrightInformation":"\u00a9 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association."},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Komaki","ForeName":"Hirofumi","Initials":"H","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0002-0659-1417"}],"AffiliationInfo":[{"Affiliation":"Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Takeshima","ForeName":"Yasuhiro","Initials":"Y","AffiliationInfo":[{"Affiliation":"Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Matsumura","ForeName":"Tsuyoshi","Initials":"T","AffiliationInfo":[{"Affiliation":"Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ozasa","ForeName":"Shiro","Initials":"S","AffiliationInfo":[{"Affiliation":"Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Kumamoto, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Funato","ForeName":"Michinori","Initials":"M","AffiliationInfo":[{"Affiliation":"Department of Pediatrics, National Hospital Organization Nagara Medical Center, Gifu, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Takeshita","ForeName":"Eri","Initials":"E","AffiliationInfo":[{"Affiliation":"Department of Child Neurology, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Iwata","ForeName":"Yasuyuki","Initials":"Y","AffiliationInfo":[{"Affiliation":"Department of Rehabilitation, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yajima","ForeName":"Hiroyuki","Initials":"H","AffiliationInfo":[{"Affiliation":"Department of Rehabilitation, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Egawa","ForeName":"Yoichi","Initials":"Y","AffiliationInfo":[{"Affiliation":"Global Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Toramoto","ForeName":"Takuya","Initials":"T","AffiliationInfo":[{"Affiliation":"Global Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Tajima","ForeName":"Masaya","Initials":"M","AffiliationInfo":[{"Affiliation":"Global Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Takeda","ForeName":"Shinichi","Initials":"S","AffiliationInfo":[{"Affiliation":"National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan."}]}]},"Language":["eng"],"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D017426"},"@text":"Clinical Trial, Phase I"},{"@attributes":{"UI":"D017427"},"@text":"Clinical Trial, Phase II"},{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D016448"},"@text":"Multicenter Study"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2020","Month":"12","Day":"07"}]},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Ann Clin Transl Neurol","NlmUniqueID":"101623278","ISSNLinking":"2328-9503"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D016189"},"@text":"Dystrophin"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D009841"},"@text":"Oligonucleotides"}},{"RegistryNumber":"SXA7YP6EKX","NameOfSubstance":{"@attributes":{"UI":"C000654848"},"@text":"viltolarsen"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D002648","MajorTopicYN":"N"},"@text":"Child"}},{"DescriptorName":{"@attributes":{"UI":"D002675","MajorTopicYN":"N"},"@text":"Child, Preschool"}},{"DescriptorName":{"@attributes":{"UI":"D016189","MajorTopicYN":"N"},"@text":"Dystrophin"},"QualifierName":[{"@attributes":{"UI":"Q000187","MajorTopicYN":"Y"},"@text":"drug effects"},{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D007564","MajorTopicYN":"N","Type":"Geographic"},"@text":"Japan"}},{"DescriptorName":{"@attributes":{"UI":"D008297","MajorTopicYN":"N"},"@text":"Male"}},{"DescriptorName":{"@attributes":{"UI":"D020388","MajorTopicYN":"N"},"@text":"Muscular Dystrophy, Duchenne"},"QualifierName":[{"@attributes":{"UI":"Q000188","MajorTopicYN":"Y"},"@text":"drug therapy"},{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"},{"@attributes":{"UI":"Q000503","MajorTopicYN":"N"},"@text":"physiopathology"}]},{"DescriptorName":{"@attributes":{"UI":"D009841","MajorTopicYN":"N"},"@text":"Oligonucleotides"},"QualifierName":[{"@attributes":{"UI":"Q000008","MajorTopicYN":"N"},"@text":"administration & dosage"},{"@attributes":{"UI":"Q000009","MajorTopicYN":"N"},"@text":"adverse effects"},{"@attributes":{"UI":"Q000493","MajorTopicYN":"N"},"@text":"pharmacokinetics"},{"@attributes":{"UI":"Q000494","MajorTopicYN":"Y"},"@text":"pharmacology"}]},{"DescriptorName":{"@attributes":{"UI":"D017063","MajorTopicYN":"N"},"@text":"Outcome Assessment, Health Care"}}]},"CoiStatement":"H.K. has received grants from Taiho, Pfizer Japan, Nippon Shinyaku, Daiichi Sankyo, Chugai, PTC Therapeutics; and personal fees from Sarepta Therapeutics. Y.T. has received grants from Nippon Shinyaku; and personal fees from Daiichi Sankyo and Biogen. T.M. has received grants from Nippon Shinyaku. S.O. has received grants from Nippon Shinyaku, Biogen, and PTC Therapeutics. M.F. has received grants from Nippon Shinyaku and Taiho. E.T. has received grants from Taiho, Nippon Shinyaku, Daiichi Sankyo, and Takeda; and personal fees from Pfizer Japan. Y.I. has received grants from Taiho, Nippon Shinyaku, and Daiichi Sankyo; and personal fees from Astellas Pharma. H.Y. has received grants from Taiho, Nippon Shinyaku, and Daiichi Sankyo; and personal fees from Biogen. S.T. is an officer and board member of the National Center of Neurology and Psychiatry; and has received grants from Nippon Shinyaku, Daiichi Sankyo and The Noguchi Institute. Y.E., M.T., and T.T. are employees of Nippon Shinyaku Co., Ltd."},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2020","Month":"5","Day":"27"},{"@attributes":{"PubStatus":"revised"},"Year":"2020","Month":"10","Day":"1"},{"@attributes":{"PubStatus":"accepted"},"Year":"2020","Month":"10","Day":"3"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2020","Month":"12","Day":"8","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2021","Month":"11","Day":"3","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"entrez"},"Year":"2020","Month":"12","Day":"7","Hour":"17","Minute":"14"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2020","Month":"12","Day":"7"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"33285037"},{"@attributes":{"IdType":"pmc"},"@text":"PMC7732240"},{"@attributes":{"IdType":"doi"},"@text":"10.1002\/acn3.51235"}]},"ReferenceList":[{"Reference":[{"Citation":"Guiraud S, Chen H, Burns DT, Davies KE. 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