{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:31:55Z","timestamp":1785461515776,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>HTLV\u20101 infection causes HTLV\u20101\u2010associated myelopathy\/tropical spastic paraparesis (HAM\/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of <jats:sc>l\u2010<\/jats:sc>arginine in patients with HAM\/TSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This open\u2010label, single\u2010arm, Phase 2 study enrolled patients diagnosed with HAM\/TSP. Patients received <jats:sc>l<\/jats:sc>\u2010arginine at a dose of 20\u2009g orally for 1\u2009week and were followed\u2010up for 3\u2009weeks. The primary endpoint was change in walking speed in the 10\u2010m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study enrolled 20 patients (13 [65%] female) with a mean age of 67.8\u2009years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time <jats:sc>\u2212<\/jats:sc>3.5%, 95% CI <jats:sc>\u2212<\/jats:sc>10.8% to 3.7%; <jats:italic>P<\/jats:italic>\u00a0=\u20090.32), a significant improvement was detected between baseline and Day 14 (<jats:sc>\u2212<\/jats:sc>9.4%, 95% CI <jats:sc>\u2212<\/jats:sc>16.6% to <jats:sc>\u2212<\/jats:sc>2.2%; <jats:italic>P<\/jats:italic>\u00a0=\u20090.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (<jats:sc>\u2212<\/jats:sc>9.1%, 95% CI <jats:sc>\u2212<\/jats:sc>15.5% to <jats:sc>\u2212<\/jats:sc>2.7%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.01), and in neopterin concentration in CSF (<jats:sc>\u2212<\/jats:sc>2.1\u00a0pmol\/mL, 95% CI <jats:sc>\u2212<\/jats:sc>3.8 to <jats:sc>\u2212<\/jats:sc>0.5; <jats:italic>P<\/jats:italic>\u00a0=\u20090.01). Adverse events were infrequent, mild, and resolved rapidly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:sc>l\u2010<\/jats:sc>arginine therapy improved motor function and decreased CSF inflammatory markers. <jats:sc>l<\/jats:sc>\u2010arginine thus represents a promising therapeutic option for patients with HAM\/TSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration Number<\/jats:title><jats:p>UMIN000023854.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51715","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T14:40:10Z","timestamp":1671720010000},"page":"237-245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of <scp>l<\/scp>\u2010Arginine treatment in patients with <scp>HTLV\u20101\u2010associated<\/scp> neurological disease"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-7769","authenticated-orcid":false,"given":"Satoshi","family":"Nozuma","sequence":"first","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusei","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Sakiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hashiguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Michizono","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection Kagoshima University  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kodama","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection Kagoshima University  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection Kagoshima University  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Yamano","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Moritoyo","sequence":"additional","affiliation":[{"name":"Clinical Research Promotion Center The University of Tokyo Hospital  Bunkyo\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Kubota","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection Kagoshima University  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)91298-5"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(85)92734-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1789.2000.00320.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000141"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086144"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0451-x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.12"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-020-00881-w"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.116.234740"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170808120633"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9494-x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000151976.60624.01"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001176"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa115"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.5607\/en.2016.25.1.24"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.12.039"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1983.63.4.1481"},{"key":"e_1_2_12_20_1","volume-title":"Review of WHO Kagoshima Meeting and Diagnostic Guidelines for HAM\/TSP","author":"Osame M","year":"1990"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ptj\/67.2.206"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.4.1016"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2006.02.042"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002479"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01651"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704827"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-003-1181-9"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00181"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90012-A"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880170812"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-015-0275-7"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2165\/11538590-000000000-00000"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00019"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.54.5444"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.5.1633"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51715","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51715","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T12:04:10Z","timestamp":1692273850000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,22]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/acn3.51715"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51715","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,22]]},"assertion":[{"value":"2022-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}