{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:40:34Z","timestamp":1783698034354,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T00:00:00Z","timestamp":1623542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013927","name":"National MPS Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to evaluate the efficacy of high dose genistein aglycone in Sanfilippo syndrome (mucopolysaccharidosis type III). High doses of genistein aglycone have been shown to correct neuropathology and hyperactive behaviour in mice, but efficacy in humans is uncertain. This was a single centre, double\u2010blinded, randomised, placebo\u2010controlled study with open\u2010label extension phase. Randomised participants received either 160\u2009mg\/kg\/day genistein aglycone or placebo for 12\u2009months; subsequently all participants received genistein for 12\u2009months. The primary outcome measure was the change in heparan sulfate concentration in cerebrospinal fluid (CSF), with secondary outcome measures including heparan sulfate in plasma and urine, total glycosaminoglycans in urine, cognitive and adaptive behaviour scores, quality of life measures and actigraphy. Twenty\u2010one participants were randomised and 20 completed the placebo\u2010controlled phase. After 12\u2009months of treatment, the CSF heparan sulfate concentration was 5.5% lower in the genistein group (adjusted for baseline values), but this was not statistically significant (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.26), and CSF heparan sulfate increased in both groups during the open\u2010label extension phase. Reduction of urinary glycosaminoglycans was significantly greater in the genistein group (32.1% lower than placebo after 12\u2009months, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0495). Other biochemical and clinical parameters showed no significant differences between groups. High dose genistein aglycone (160\u2009mg\/kg\/day) was not associated with clinically meaningful reductions in CSF heparan sulfate and no evidence of clinical efficacy was detected. However, there was a statistically significant reduction in urine glycosaminoglycans. These data do not support the use of genistein aglycone therapy in mucopolysaccharidosis type III. High dose genistein aglycone does not lead to clinically meaningful reductions in biomarkers or improvement in neuropsychological outcomes in mucopolysaccharidosis type III.<\/jats:p>","DOI":"10.1002\/jimd.12407","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T09:40:18Z","timestamp":1622194818000},"page":"1248-1262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["High dose genistein in Sanfilippo syndrome: A randomised controlled trial"],"prefix":"10.1002","volume":"44","author":[{"given":"Arunabha","family":"Ghosh","sequence":"first","affiliation":[{"name":"Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital  Manchester UK"},{"name":"Stem Cell and Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Rust","sequence":"additional","affiliation":[{"name":"Paediatric Psychosocial Service Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kia","family":"Langford\u2010Smith","sequence":"additional","affiliation":[{"name":"Stem Cell and Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weisberg","sequence":"additional","affiliation":[{"name":"Paediatric Psychosocial Service Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Canal","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Breen","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hepburn","sequence":"additional","affiliation":[{"name":"Wellcome Trust Children's Clinical Research Facility, Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Tylee","sequence":"additional","affiliation":[{"name":"Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Amsterdam UMC University of Amsterdam  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Vail","sequence":"additional","affiliation":[{"name":"Centre for Biostatistics, School of Health Sciences University of Manchester  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Wijburg","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, location Academic Medical Center  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Stem Cell and Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Parker","sequence":"additional","affiliation":[{"name":"Stem Cell and Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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