{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:13:19Z","timestamp":1791112399346,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["R21NS078333"],"award-info":[{"award-number":["R21NS078333"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["R01NS020253"],"award-info":[{"award-number":["R01NS020253"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CURE"},{"name":"Heffer Family Foundation"},{"name":"Siegel Family Foundation"},{"name":"The Einstein CTSA award","award":["NCRR UL1-RR025750"],"award-info":[{"award-number":["NCRR UL1-RR025750"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development"},{"name":"National Institutes of Health (NIH) Award","award":["P30HD071593"],"award-info":[{"award-number":["P30HD071593"]}]},{"name":"NIH MSTP training grant","award":["T32-GM007288"],"award-info":[{"award-number":["T32-GM007288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Infantile spasms (<jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>) have poor outcomes and limited treatment options, including vigabatrin, a \u03b3\u2010aminobutyric acid (<jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>) aminotransferase inactivator. Vigabatrin has been associated with retinal toxicity. A high affinity vigabatrin analogue (<jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115; Catalyst Pharmaceutical Partners, Inc., Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test the efficacy of <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 in reducing spasms and its tolerability in the multiple\u2010hit rat model of <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>, in which daily vigabatrin reduced spasms for only one\u00a0day, but was not well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male rats were treated with the protocol of the multiple\u2010hit model of <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content> on postnatal day 3 (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>3). Using a randomized, blinded, vehicle\u2010controlled, dose\u2010response study design, <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 (0.1, 1, or 5\u00a0mg\/kg intraperitoneally [i.p.]) or vehicle was given daily (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>4\u201312) or as a single injection (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>7) after spasm onset. Intermittent video\u2010 or video\u2010electroencephalography (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>) monitoring was done. Secondary end points included the following: daily weights, survival, performance on open field activity, surface righting time, and negative geotaxis (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>3\u201320), horizontal bar (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>13\u201320), and Barnes maze (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>16\u201319). Statistics used a linear mixed model of raw or normalized log\u2010transformed data, taking into account the repeated observations on each animal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The lower <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 doses (0.1\u20131\u00a0mg\/kg\/day, <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>4\u201312) reduced spasms between <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>6 and 7 without increasing mortality. <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 at 5\u00a0mg\/kg\/day (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>4\u201312) reduced spasms earlier (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>5), but was eventually lethal. A single <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 injection (1\u00a0mg\/kg, i.p.) decreased electroclinical spasms acutely but transiently. <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 transiently improved the probability to &gt;50% reduction of spasms, but did not accelerate spasm cessation. <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 did not alter neurodevelopmental outcomes or visuospatial learning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We provide proof\u2010of\u2010concept evidence that <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115, a vigabatrin analogue, decreases spasms in the multiple\u2010hit rat model of <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content> at considerably lower and better tolerated doses than vigabatrin did in our previous studies. Further optimization of the treatment protocol is needed. <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>\u2010115 may be a promising new candidate treatment for <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content> with better tolerability than vigabatrin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12424","type":"journal-article","created":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T14:05:42Z","timestamp":1382969142000},"page":"94-102","source":"Crossref","is-referenced-by-count":55,"title":["<scp>CPP<\/scp>\u2010115, a vigabatrin analogue, decreases spasms in the multiple\u2010hit rat model of infantile spasms"],"prefix":"10.1111","volume":"55","author":[{"given":"Stephen W.","family":"Briggs","sequence":"first","affiliation":[{"name":"Saul R. Korey Department of Neurology Albert Einstein College of Medicine Bronx New York U.S.A"},{"name":"Laboratory of Developmental Epilepsy and Dominick P. Purpura Department of Neuroscience Albert Einstein College of Medicine Bronx New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhu","family":"Mowrey","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Hall","sequence":"additional","affiliation":[{"name":"Saul R. Korey Department of Neurology Albert Einstein College of Medicine Bronx New York U.S.A"},{"name":"Division of Biostatistics Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristea S.","family":"Galanopoulou","sequence":"additional","affiliation":[{"name":"Saul R. Korey Department of Neurology Albert Einstein College of Medicine Bronx New York U.S.A"},{"name":"Laboratory of Developmental Epilepsy and Dominick P. Purpura Department of Neuroscience Albert Einstein College of Medicine Bronx New York U.S.A"},{"name":"Montefiore\/Einstein Epilepsy Center Bronx New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004691-200311000-00004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.11.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000127773.72699.C8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02657.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318259e2cf"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656560903451690"},{"key":"e_1_2_7_8_1","first-page":"731","article-title":"Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms","volume":"6","author":"Lerner JT","year":"2010","journal-title":"Neuropsychiatr Dis Treat"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(99)00082-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2011.01599.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.314.7075.180"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.3.614"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90112-2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(92)90080-D"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(90)90092-A"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809348796"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201231w"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm034162s"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201650r"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03173.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.03.021"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20225"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00966667"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(81)90005-5"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00318343"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6768130"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02772.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01961.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01589.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2012.01684.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.01004.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21526"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317650-000000000-00000"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2009.160606"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70199-X"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90624-D"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.04.013"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12295"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.12.005"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12424","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12424","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T22:07:08Z","timestamp":1696370828000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,28]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1111\/epi.12424"],"URL":"https:\/\/doi.org\/10.1111\/epi.12424","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,28]]}}}