{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:11:23Z","timestamp":1788631883934,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Classic homocystinuria (HCU) is an inherited disorder characterized by elevated homocysteine (Hcy) in plasma and tissues resulting from cystathionine \u03b2\u2010synthase (CBS) deficiency. There is no cure, and patients are predominantly managed by methionine\u2010restricted diet (MRD) to limit the production of Hcy. In this study, we used the I278T mouse model of HCU to evaluate the long\u2010term impact of a novel enzyme replacement therapy [truncated human CBS C15S mutant modified with linear 20\u2010kDa\n                    <jats:italic>N<\/jats:italic>\n                    \u2010hydroxysuccinimide ester polyethylene glycol (OT\u201058)] on clinical end points relevant to human patients with HCU. In addition, we compared its efficacy on a background of either MRD or normal methionine intake [regular diet (REG)] to that of MRD alone. We found that, compared with untreated I278T mice, OT\u201058 treatment of I278T mice fed with the REG diet resulted in a 90% decrease in plasma Hcy concentrations and correction of learning\/cognition, endothelial dysfunction, hemostasis, bone mineralization, and body composition. On background of the MRD, OT\u201058 performed equally well with plasma Hcy entirely normalized. The MRD alone decreased plasma Hcy by 67% and corrected the HCU phenotype in I278T mice. However, the MRD increased anxiety and reduced bone mineral content in both I278T mice and wild\u2010type controls. This study shows that OT\u201058 is a highly efficacious novel treatment for HCU on the background of either normal or restricted methionine intake.\u2014Majtan, T., Park, I., Cox, A., Branchford, B. R., di Paola, J., Bublil, E. M., Kraus, J. P. Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine\u2010restricted diet or enzyme replacement therapy. FASEB J. 33, 12477\u201312486 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901203r","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T22:47:36Z","timestamp":1566859656000},"page":"12477-12486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine\u2010restricted diet or enzyme replacement therapy"],"prefix":"10.1096","volume":"33","author":[{"given":"Tomas","family":"Majtan","sequence":"first","affiliation":[{"name":"Section of Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insun","family":"Park","sequence":"additional","affiliation":[{"name":"Section of Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allaura","family":"Cox","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology Department of Pediatrics School of Medicine"},{"name":"Hemophilia and Thrombosis Center University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Branchford","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology Department of Pediatrics School of Medicine"},{"name":"Hemophilia and Thrombosis Center University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"di Paola","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology Department of Pediatrics School of Medicine"},{"name":"Hemophilia and Thrombosis Center University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erez M.","family":"Bublil","sequence":"additional","affiliation":[{"name":"Orphan Technologies Limited Rapperswil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P.","family":"Kraus","sequence":"additional","affiliation":[{"name":"Section of Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"2007","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Mudd S. 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