{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:08:32Z","timestamp":1790885312101,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis Pharma AG Switzerland"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy.\n This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case\u2013control design.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>At the University of Basel Children\u2019s Hospital, Basel, Switzerland, children with RS were included if they were older than 6\u00a0years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation. Participants were observed 6\u00a0months before and after treatment and received 12\u00a0months of fingolimod treatment. Serum samples of 50 children without RS served as reference for brain-derived neurotrophic factor (BDNF) measurements. Primary outcome measures were safety and efficacy, the latter measured by change in levels of BDNF in serum\/CSF (cerebrospinal fluid) and change in deep gray matter volumes measured by magnetic resonance imaging (MRI). Secondary outcome measure was efficacy measured by change in clinical scores [Vineland Adaptive Behaviour Scale (VABS), Rett Severity Scale (RSSS) and Hand Apraxia Scale (HAS)].<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Six children with RS (all girls, mean and SD age 11.3\u2009\u00b1\u20093.1\u00a0years) were included. Serum samples of 50 children without RS (25 females, mean and SD age 13.5\u2009\u00b1\u20093.9\u00a0years) served as reference for BDNF measurements. No serious adverse events occurred. Primary and secondary outcome measures were not met. CSF BDNF levels were associated with all clinical scores: RSSS (estimate\u2009\u2212\u20090.04, mult.effect 0.96, CI [0.94; 0.98], p\u2009=\u20090.03), HAS (estimate\u2009\u2212\u20090.09, mult.effect 0.91, CI [0.89; 0.94], p\u2009&lt; \u20090.01) and VABS (communication: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p\u2009&lt;\u20090.01\/daily living: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p\u2009&lt;\u20090.01\/social skills: estimate 0.07, mult.effect 1.08, CI [1.05; 1.11], p\u2009&lt;\u20090.01\/motoric skills: estimate 0.04, mult.effect 1.04, CI [1.03; 1.06], p\u2009=\u20090.02).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In children with RS, treatment with fingolimod was safe. The study did not provide supportive evidence for an effect of fingolimod on clinical, laboratory, and imaging measures. CSF BDNF levels were associated with clinical scores, indicating a need to further evaluate its potential as a biomarker for RS. This finding should be further validated in independent patient groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial Registration<\/jats:title>\n                <jats:p>Clinical Trials.gov NCT02061137, registered on August 27th 2013, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02061137\">https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02061137<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-020-01655-7","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T22:03:49Z","timestamp":1609970629000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Fingolimod in children with Rett syndrome: the FINGORETT study"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1315-4100","authenticated-orcid":false,"given":"Yvonne","family":"Naegelin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Sch\u00e4delin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre N.","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Magon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Amann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Barro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Paolo","family":"Ramelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Heesom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves-Alain","family":"Barde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"issue":"37","key":"1655_CR1","first-page":"723","volume":"116","author":"A Rett","year":"1966","unstructured":"Rett A. 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Written informed consent was obtained from all parents of participating children [RS (all) and HC (if children were younger than 14)] and from all healthy children (age 6\u201310 oral informed consent only, but written informed consent from parents).The study was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Yvonne Naegelin\u2019s employer, the University Hospital Basel, received payments for lecturing from Celgene GmbH and Teva Pharma AG that were exclusively used for research support, not related to this study. Jens Kuhle received speaker fees, research support, travel support, and\/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_189140\/1), University of Basel, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi. Alexandre N. Datta has served on scientific advisory boards for UCB, Eisai, and Nutricia. He has consultancy activities for Roche, Idorsia, Neurocrine, and Epilog. He has received funding for travel from UCB, Sanofi, Eisai, and Nutricia. Stefano Magon is an employee of F. Hoffmann-La Roche Ltd. Roche was not involved in the study. Ludwig Kappos\u2019s institution (University Hospital Basel) received in the last 3\u00a0years and used exclusively for research support at the Department: steering committee, advisory board, consultancy fees and support of educational activities from: Actelion, Allergan, Almirall, Baxalta, Bayer, Biogen, Celgene\/Receptos, CSL-Behring, Desitin, Excemed, Eisai,Genzyme, Japan Tobacco, Merck, Minoryx, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi Aventis, Santhera, Teva, and license fees for Neurostatus-UHB products; the Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, Innosuisse, the European Union, and Roche Research Foundations. Sabine Sch\u00e4delin, Michael Amann, Christian Barro, Gian Paolo Ramelli, Kate Heesom, Yves Alain Barde, and Peter Weber have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}