{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:26:09Z","timestamp":1791293169479,"version":"4.1.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,3,25]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>This paper provides unique insights into mechanism-based therapeutics for Rett syndrome (RTT), a devastating neurodevelopmental disorder. This clinical trial was based on pioneer preclinical work from the laboratory of M.S. Outcome measures include clinical instruments, standardized behavioral measures, and biomarkers, the latter being not only objective but also applicable to experimental studies. We believe this work will a have major impact on the understanding and treatment of RTT, as well as other neurodevelopmental disorders.<\/jats:p>","DOI":"10.1073\/pnas.1311141111","type":"journal-article","created":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T21:45:00Z","timestamp":1394660700000},"page":"4596-4601","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome"],"prefix":"10.1073","volume":"111","author":[{"given":"Omar S.","family":"Khwaja","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"},{"name":"Neurosciences Translational Medicine, Pharma Research and Early Development, F. Hoffmann\u2013La Roche AG, 4070 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"},{"name":"Division of Neurology, Children\u2019s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine V.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Perioperative and Pain Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Divisions of Emergency Medicine and Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, ON, Canada M5G 1X8;"},{"name":"Division of Emergency Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Charles A.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Development Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Vogel-Farley","sequence":"additional","affiliation":[{"name":"Division of Development Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geneva","family":"DeGregorio","sequence":"additional","affiliation":[{"name":"Division of Development Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid A.","family":"Holm","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, and The Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umakanth","family":"Khatwa","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kush","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"},{"name":"Clinical Research Center, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre M.","family":"Finnegan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole G.","family":"Cantwell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Walco","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Rappaport","sequence":"additional","affiliation":[{"name":"Division of Development Medicine, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Gregas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"},{"name":"Clinical Research Center, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raina N.","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Boston Children\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mriganka","family":"Sur","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,3,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22124"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10020"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2013.01.014"},{"key":"e_1_3_3_4_2","volume-title":"New Developments in Treatment for Neurodevelopmental Disorders: Targeting Neurobiological Mechanisms","author":"Tarquinio DC","year":"2014","unstructured":"DC Tarquinio, WE Kaufmann, Targeted treatments in Rett syndrome. New Developments in Treatment for Neurodevelopmental Disorders: Targeting Neurobiological Mechanisms, eds R Hagerman, R Hendren (Oxford Univ Press, New York, 2014)."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10022"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2004.10.008"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138389"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws096"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32834c9251"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/1574889811308020004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e3180302078"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep00045"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812394106"},{"key":"e_1_3_3_14_2","article-title":"Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome","author":"Castro J","year":"2012","unstructured":"J Castro, et al., Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome. Soc Neurosci, 2012 (abstr). (2012).","journal-title":"Soc Neurosci"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2012.04.010"},{"key":"e_1_3_3_16_2","volume-title":"Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications","author":"Gabrielsson J","year":"2007","unstructured":"J Gabrielsson, D Weiner Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications (Swedish Pharmaceutical Press, 4th Ed, Stockholm, 2007).","edition":"4"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.2001.450116.x"},{"key":"e_1_3_3_18_2","volume-title":"The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications","author":"Iber C","year":"2007","unstructured":"C Iber The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications (American Academy of Sleep Medicine, Westchester, IL, 2007)."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.4.384"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200411000-00005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22154"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-7610.00236"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.2011.01404.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:JADD.0000005999.27178.55"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11689-010-9067-y"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1037\/0021-843X.115.4.715"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00137-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2012.06.002"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.05.029"},{"key":"e_1_3_3_30_2","first-page":"679801","article-title":"IGF1 as a potential treatment for Rett syndrome: Safety assessment in six Rett patients","volume":"2012","author":"Pini G","year":"2012","unstructured":"G Pini, et al., IGF1 as a potential treatment for Rett syndrome: Safety assessment in six Rett patients. Autism Res Treat 2012, 679801 (2012).","journal-title":"Autism Res Treat"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt111"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.11.007"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2012-0418"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1291242"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02499.x"},{"key":"e_1_3_3_36_2","unstructured":"Tercica Inc. (2007) Investigator\u2019s Brochure: Recombinant Human Insulin-Like Growth Factor-1 (Tercica Inc. a subsidiary of the Ipsen Group Brisbane CA)."},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161211797415995"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-008-0136-5"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1993.tb12918.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986706778201602"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.06.009"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62226-X"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.001"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004218"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001708"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004214"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2009.2038487"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2006.02.011"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(58)90053-1"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/dev.10053"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1162\/0898929042304723"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1311141111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:56:12Z","timestamp":1649804172000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1311141111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,12]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,3,25]]}},"alternative-id":["10.1073\/pnas.1311141111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1311141111","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718308943.793511143","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,12]]},"assertion":[{"value":"2014-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}