{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T20:22:04Z","timestamp":1787948524138,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20lm0203086h0002"],"award-info":[{"award-number":["20lm0203086h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS\u2010089\/NCNP\u201002 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is an open\u2010label, dose\u2010escalation, two\u2010center phase I\/II trial in ambulant patients with DMD, presence of an out\u2010of\u2010frame deletion, and a mutation amenable to exon 44 skipping. Part 1 is a stepwise dose\u2010finding stage (4\u2009weeks) during which NS\u2010089\/NCNP\u201002 will be administered intravenously at four dose levels once weekly (1.62, 10, 40, and 80\u2009mg\/kg); Part 2 is a 24\u2010week evaluation period based on the dosages determined during Part 1. The primary (safety) endpoints are the results of physical examinations, vital signs, 12\u2010lead electrocardiogram and echocardiography tests, and adverse event reporting. Secondary endpoints include expression of dystrophin protein, motor function assessment, exon 44 skipping efficiency, plasma and urinary NS\u2010089\/NCNP\u201002 concentrations, and changes in blood creatine kinase levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Exon\u2010skipping therapy using ASOs shows promise in selected patients, and this first\u2010in\u2010human study is expected to provide critical information for subsequent clinical development of NS\u2010089\/NCNP\u201002.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.12335","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T02:46:43Z","timestamp":1680576403000},"page":"277-286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Systemic administration of the antisense oligonucleotide\n   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