{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:38:13Z","timestamp":1792165093530,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Zafgen, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      There are no treatments for the extreme hyperphagia and obesity in Prader\u2013Willi syndrome (\n                      <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>\n                      ). The\n                      <jats:styled-content style=\"fixed-case\">bestPWS<\/jats:styled-content>\n                      clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (\n                      <jats:styled-content style=\"fixed-case\">MetAP<\/jats:styled-content>\n                      2) inhibitor, beloranib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Participants with\n                      <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>\n                      (12\u201065 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15\n                      <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content>\n                      sites. Co\u2010primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (\n                      <jats:styled-content style=\"fixed-case\">HQ<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\n                      ); possible score 0\u201036] and weight by intention\u2010to\u2010treat.\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      registration:\n                      <jats:styled-content style=\"fixed-case\">NCT02179151<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One\u2010hundred and seven participants were included in the intention\u2010to\u2010treat analysis: placebo (\n                      <jats:italic>n<\/jats:italic>\n                      = 34); 1.8 mg beloranib (\n                      <jats:italic>n<\/jats:italic>\n                      = 36); or 2.4 mg beloranib (\n                      <jats:italic>n<\/jats:italic>\n                      = 37). Improvement (reduction) in\n                      <jats:styled-content style=\"fixed-case\">HQ\u2010CT<\/jats:styled-content>\n                      total score was greater in the 1.8 mg (mean difference \u22126.3, 95%\n                      <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                      \u22129.6 to \u22123.0;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      = .0003) and 2.4 mg beloranib groups (\u22127.0, 95% CI \u221210.5 to \u22123.6;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference \u2212 8.2%, 95% CI \u221210.8 to \u22125.6;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      &lt; .0001) and 2.4 mg beloranib (\u22129.5%, 95% CI \u221212.1 to \u22126.8;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      &lt; .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib\u2010treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">MetAP2<\/jats:styled-content>\n                      inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia\u2010related behaviours and weight loss in participants with\n                      <jats:styled-content style=\"fixed-case\">PWS<\/jats:styled-content>\n                      . Although investigation of beloranib has ceased, inhibition of\n                      <jats:styled-content style=\"fixed-case\">MetAP2<\/jats:styled-content>\n                      is a novel mechanism for treating hyperphagia and obesity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13021","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T04:02:45Z","timestamp":1496030565000},"page":"1751-1761","source":"Crossref","is-referenced-by-count":108,"title":["Effects of\n                    <scp>MetAP2<\/scp>\n                    inhibition on hyperphagia and body weight in Prader\u2013Willi syndrome: A randomized, double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"19","author":[{"given":"Shawn E.","family":"McCandless","sequence":"first","affiliation":[{"name":"UH Cleveland Medical Center and Case Western Reserve University  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Yanovski","sequence":"additional","affiliation":[{"name":"Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Miller","sequence":"additional","affiliation":[{"name":"University of Florida  Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Fu","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne M.","family":"Bird","sequence":"additional","affiliation":[{"name":"UCSD Rady Children's Hospital  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parisa","family":"Salehi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology &amp; Diabetes Seattle Children's Hospital  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado  Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Stafford","sequence":"additional","affiliation":[{"name":"Children's Hospital Boston  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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