{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:34:41Z","timestamp":1791441281937,"version":"4.3.3"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Research and Development","award":["LIDER 20\/59\/L-3\/11\/NCBR\/2012"],"award-info":[{"award-number":["LIDER 20\/59\/L-3\/11\/NCBR\/2012"]}]},{"name":"National Center for Research and Development","award":["TEAM\/2008-2\/7"],"award-info":[{"award-number":["TEAM\/2008-2\/7"]}]},{"DOI":"10.13039\/501100001870","name":"Foundation for Polish Science Team","doi-asserted-by":"publisher","award":["LIDER 20\/59\/L-3\/11\/NCBR\/2012"],"award-info":[{"award-number":["LIDER 20\/59\/L-3\/11\/NCBR\/2012"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Foundation for Polish Science Team","doi-asserted-by":"publisher","award":["TEAM\/2008-2\/7"],"award-info":[{"award-number":["TEAM\/2008-2\/7"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by \u03b1-L-iduronidase deficiency. The standard treatment, enzyme replacement therapy with laronidase, has limited effectiveness in treating neurological symptoms due to poor blood\u2013brain barrier penetration. An alternative is substrate reduction therapy using molecules, such as genistein, which crosses this barrier. This study evaluated the effectiveness of a combination of laronidase and genistein in a mouse model of MPS I. Over 12 weeks, MPS I and wild-type mice received laronidase, genistein, or both. Glycosaminoglycan (GAG) storage in visceral organs and the brain, its excretion in urine, and the serum level of the heparin cofactor II\u2013thrombin (HCII-T) complex, along with behavior, were assessed. The combination therapy resulted in reduced GAG storage in the heart and liver, whereas genistein alone reduced the brain GAG storage. Laronidase and combination therapy decreased liver and spleen weights and significantly reduced GAG excretion in the urine. However, this therapy negated some laronidase benefits in the HCII-T levels. Importantly, the combination therapy improved the behavior of female mice with MPS I. These findings offer valuable insights for future research to optimize MPS I treatments.<\/jats:p>","DOI":"10.3390\/ijms25042371","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T05:39:56Z","timestamp":1708321196000},"page":"2371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy of a Combination Therapy with Laronidase and Genistein in Treating Mucopolysaccharidosis Type I in a Mouse Model"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5586-4354","authenticated-orcid":false,"given":"Marcelina","family":"Malinowska","sequence":"first","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Biology, University of Gda\u0144sk, Wita Stwosza 59, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0977-9542","authenticated-orcid":false,"given":"Wioletta","family":"Nowicka","sequence":"additional","affiliation":[{"name":"InviMed Ferility Clinics, 10 Lutego 16, 81-364 Gdynia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5168-0232","authenticated-orcid":false,"given":"Anna","family":"Kloska","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Biology, University of Gda\u0144sk, Wita Stwosza 59, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4042-7466","authenticated-orcid":false,"given":"Grzegorz","family":"W\u0119grzyn","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Biology, University of Gda\u0144sk, Wita Stwosza 59, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Jak\u00f3bkiewicz-Banecka","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Biology, University of Gda\u0144sk, Wita Stwosza 59, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kubaski, F., de Oliveira Poswar, F., Michelin-Tirelli, K., Matte, U.d.S., Horovitz, D.D., Barth, A.L., Baldo, G., Vairo, F., and Giugliani, R. 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