{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T23:17:35Z","timestamp":1788650255206,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["R01 FD003523"],"award-info":[{"award-number":["R01 FD003523"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001951","name":"Angelman Syndrome Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001951","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005615","name":"Beth Israel Deaconess Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54 HD061222"],"award-info":[{"award-number":["U54 HD061222"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium\/calmodulin\u2010dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long\u2010term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium\/calmodulin\u2010dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi\u2010center double\u2010blind randomized placebo\u2010controlled 1\u2010year trial of levodopa \/ carbidopa with either 10 or 15\u2009mg\/kg\/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1\u2010year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1\u2010year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well\u2010tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38457","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T06:12:51Z","timestamp":1506319971000},"page":"1099-1107","source":"Crossref","is-referenced-by-count":28,"title":["A randomized controlled trial of levodopa in patients with Angelman syndrome"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-6149","authenticated-orcid":false,"given":"Wen\u2010Hann","family":"Tan","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital; Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne M.","family":"Bird","sequence":"additional","affiliation":[{"name":"Genetics \/ Dysmorphology Rady Children's Hospital San Diego; Department of Pediatrics University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Sadhwani","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Boston Children's Hospital; 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