{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:07:21Z","timestamp":1787238441595,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009017","name":"ALS Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009017","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NeuroSense Therapeutics"},{"name":"The Israeli Ministry of Science and Technology"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy of a fixed\u2010dose combination of two approved drugs, Ciprofloxacin and Celecoxib, as a potential therapeutic treatment for amyotrophic lateral sclerosis (ALS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Toxicity and efficacy of Ciprofloxacin and Celecoxib were tested, each alone and in distinct ratio combinations in SOD1 G93R transgenic zebrafish model for ALS. Quantification of swimming measures following stimuli, measurements of axonal projections from the spinal cord, neuromuscular junction structure and morphometric analysis of microglia cells were performed in the combination\u2010 treated\n                      <jats:italic>vs<\/jats:italic>\n                      nontreated mutant larvae. Additionally, quantifications of touch\u2010evoked locomotor escape response were conducted in treated\n                      <jats:italic>vs<\/jats:italic>\n                      nontreated zebrafish expressing the\n                      <jats:italic>TARDBP<\/jats:italic>\n                      G348C ALS variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>When administered individually, Ciprofloxacin had a mild effect and Celecoxib had no therapeutic effect. However, combined Ciprofloxacin and Celecoxib (Cipro\/Celecox) treatment caused a significant increase of\u00a0~\u00a084% in the distance the SOD1 G93R transgenic larvae swam. Additionally, Cipro\/Celecox elicited recovery of impaired motor neurons morphology and abnormal neuromuscular junction structure and preserved the ramified morphology of microglia cells in the SOD1 mutants. Furthermore, larvae expressing the TDP\u201043 mutation displayed evoked touch responses that were significantly longer in swim distance (110% increase) and significantly higher in maximal swim velocity (~44% increase) when treated with Cipro\/Celecox combination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Cipro\/Celecox combination improved locomotor and cellular deficits of ALS zebrafish models. These results identify this novel combination as effective, and may prove promising for the treatment of ALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51174","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T03:45:35Z","timestamp":1600314335000},"page":"1883-1897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Efficacy of Ciprofloxacin\/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"7","author":[{"given":"Hagit","family":"Goldshtein","sequence":"first","affiliation":[{"name":"The Dead Sea Arava Science Center Auspices of Ben Gurion University Central Arava 86815 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Muhire","sequence":"additional","affiliation":[{"name":"The Dead Sea Arava Science Center Auspices of Ben Gurion University Central Arava 86815 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Petel L\u00e9gar\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute Faculty of Medicine McGill University Montreal QC H3A 0G4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avital","family":"Pushett","sequence":"additional","affiliation":[{"name":"NeuroSense Therapeutics Ltd Medinat Hayehudim 85 Herzeliya 4676670 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Rotkopf","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biological Computing Unit Life Sciences Core Facilities Weizmann Institute of Science Rehovot 7610001 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M.","family":"Shefner","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, University of Arizona College of Medicine Phoenix, Creighton University College of Medicine Phoenix Phoenix AZ 85013 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall T","family":"Peterson","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Utah Salt Lake City UT 84112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4613-8817","authenticated-orcid":false,"given":"Gary A. 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