{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:54:38Z","timestamp":1793073278247,"version":"4.5.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Sanofi"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Allogeneic hematopoietic cell transplantation (HCT) benefits children with Hurler syndrome (MPS-IH). However, survivors remain burdened by substantial MPS-IH related residual disease. We studied the feasibility, safety and biochemical impact of augmentative recombinant intravenous enzyme replacement therapy (IV-ERT) post transplantation. Ten children with MPS-IH and \u22652 years from successful HCT underwent IV-ERT for 2 years\u2019 duration. Patients were monitored for anti-drug antibody (ADA) development, including inhibitory capacity and changes in urinary excretion of glycosaminoglycans (uGAG). Three patients demonstrated low-level ADA at baseline, though all children tolerated IV-ERT well. Eight patients developed ADA over the 2-year study, with 3 (38%) meeting criteria for an inhibitory ADA response. The aggregate cohort experienced a reduction in uGAG from baseline to study end, which was enhanced in children with low or no ADA response. Conversely, children with inhibitory ADA showed increase in uGAG over time. IV-ERT in previously transplanted children with MPS-IH appears safe and can reduce uGAG, although this is reversed by the presence of inhibitory ADA. These data show a biochemical change after initiation of post-HCT IV-ERT, but the occurrence of ADA and inhibitory antibodies are a concern and should be monitored in future efficacy trials. This trial was registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>, NCT01173016, 07\/30\/2010.<\/jats:p>","DOI":"10.1038\/s41598-019-50595-1","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T10:02:32Z","timestamp":1569924152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Post-transplant laronidase augmentation for children with Hurler syndrome: biochemical outcomes"],"prefix":"10.1038","volume":"9","author":[{"given":"Troy C.","family":"Lund","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weston P.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai Yin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Tolar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Shanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Sando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Bigger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda E.","family":"Polgreen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Orchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"50595_CR1","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1073\/pnas.69.8.2048","volume":"69","author":"G Bach","year":"1972","unstructured":"Bach, G., Friedman, R., Weissmann, B. & Neufeld, E. F. The defect in the Hurler and Scheie syndromes: deficiency of -L-iduronidase. Proc Natl Acad Sci USA 69, 2048\u20132051 (1972).","journal-title":"Proc Natl Acad Sci USA"},{"key":"50595_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-55","volume":"6","author":"MH de Ru","year":"2011","unstructured":"de Ru, M. H. et al. Enzyme replacement therapy and\/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet journal of rare diseases 6, 55, https:\/\/doi.org\/10.1186\/1750-1172-6-55 (2011).","journal-title":"Orphanet journal of rare diseases"},{"key":"50595_CR3","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.pcl.2009.11.004","volume":"57","author":"JJ Boelens","year":"2010","unstructured":"Boelens, J. J., Prasad, V. K., Tolar, J., Wynn, R. F. & Peters, C. Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. Pediatr Clin North Am 57, 123\u2013145, https:\/\/doi.org\/10.1016\/j.pcl.2009.11.004 (2010).","journal-title":"Pediatr Clin North Am"},{"key":"50595_CR4","doi-asserted-by":"publisher","first-page":"3981","DOI":"10.1182\/blood-2012-09-455238","volume":"121","author":"JJ Boelens","year":"2013","unstructured":"Boelens, J. J. et al. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood 121, 3981\u20133987, https:\/\/doi.org\/10.1182\/blood-2012-09-455238 (2013).","journal-title":"Blood"},{"issue":"6","key":"50595_CR5","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/bmt.2017.5","volume":"52","author":"S H Lum","year":"2017","unstructured":"Lum, S. H. et al. Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome. Bone Marrow Transplant, https:\/\/doi.org\/10.1038\/bmt.2017.5 (2017).","journal-title":"Bone Marrow Transplantation"},{"key":"50595_CR6","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1182\/blood-2014-11-608075","volume":"125","author":"M Aldenhoven","year":"2015","unstructured":"Aldenhoven, M. et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood 125, 2164\u20132172, https:\/\/doi.org\/10.1182\/blood-2014-11-608075 (2015).","journal-title":"Blood"},{"key":"50595_CR7","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.3324\/haematol.2011.058644","volume":"97","author":"MA Saif","year":"2012","unstructured":"Saif, M. A. et al. Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler\u2019s syndrome after pharmacological enzyme replacement therapy. Haematologica 97, 1320\u20131328, https:\/\/doi.org\/10.3324\/haematol.2011.058644 (2012).","journal-title":"Haematologica"},{"key":"50595_CR8","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ymgme.2016.01.011","volume":"117","author":"A Ghosh","year":"2016","unstructured":"Ghosh, A. et al. Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10 year combined experience of 2 centres. Mol Genet Metab 117, 373\u2013377, https:\/\/doi.org\/10.1016\/j.ymgme.2016.01.011 (2016).","journal-title":"Mol Genet Metab"},{"key":"50595_CR9","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1182\/blood-2010-04-278234","volume":"116","author":"I Visigalli","year":"2010","unstructured":"Visigalli, I. et al. Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model. Blood 116, 5130\u20135139, https:\/\/doi.org\/10.1182\/blood-2010-04-278234 (2010).","journal-title":"Blood"},{"key":"50595_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0255-4","volume":"10","author":"AR Pal","year":"2015","unstructured":"Pal, A. R. et al. Sleep disordered breathing in mucopolysaccharidosis I: a multivariate analysis of patient, therapeutic and metabolic correlators modifying long term clinical outcome. Orphanet journal of rare diseases 10, 42, https:\/\/doi.org\/10.1186\/s13023-015-0255-4 (2015).","journal-title":"Orphanet journal of rare diseases"},{"key":"50595_CR11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jpeds.2016.08.033","volume":"178","author":"S Laraway","year":"2016","unstructured":"Laraway, S. et al. Outcomes of Long-Term Treatment with Laronidase in Patients with Mucopolysaccharidosis Type I. J Pediatr 178, 219\u2013226.e211, https:\/\/doi.org\/10.1016\/j.jpeds.2016.08.033 (2016).","journal-title":"J Pediatr"},{"key":"50595_CR12","doi-asserted-by":"publisher","first-page":"e37","DOI":"10.1542\/peds.2006-2156","volume":"120","author":"JE Wraith","year":"2007","unstructured":"Wraith, J. E. et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics 120, e37\u201346, https:\/\/doi.org\/10.1542\/peds.2006-2156 (2007).","journal-title":"Pediatrics"},{"key":"50595_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ymgme.2014.10.012","volume":"114","author":"EJ Langereis","year":"2015","unstructured":"Langereis, E. J. et al. Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy. Mol Genet Metab 114, 129\u2013137, https:\/\/doi.org\/10.1016\/j.ymgme.2014.10.012 (2015).","journal-title":"Mol Genet Metab"},{"key":"50595_CR14","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.ymgme.2016.02.006","volume":"117","author":"Y Xue","year":"2016","unstructured":"Xue, Y., Richards, S. M., Mahmood, A. & Cox, G. F. Effect of anti-laronidase antibodies on efficacy and safety of laronidase enzyme replacement therapy for MPS I: A comprehensive meta-analysis of pooled data from multiple studies. Molecular genetics and metabolism 117, 419\u2013426, https:\/\/doi.org\/10.1016\/j.ymgme.2016.02.006 (2016).","journal-title":"Molecular genetics and metabolism"},{"key":"50595_CR15","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.jpeds.2008.11.005","volume":"154","author":"RF Wynn","year":"2009","unstructured":"Wynn, R. F. et al. Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. The Journal of pediatrics 154, 609\u2013611, https:\/\/doi.org\/10.1016\/j.jpeds.2008.11.005 (2009).","journal-title":"The Journal of pediatrics"},{"key":"50595_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0541-2","author":"LE Polgreen","year":"2019","unstructured":"Polgreen, L. E. et al. Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation. Pediatr Res. https:\/\/doi.org\/10.1038\/s41390-019-0541-2 (2019).","journal-title":"Pediatr Res"},{"key":"50595_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/srep38305","volume":"6","author":"GV Raymond","year":"2016","unstructured":"Raymond, G. V. et al. Elevated cerebral spinal fluid biomarkers in children with mucopolysaccharidosis I-H. Sci Rep 6, 38305, https:\/\/doi.org\/10.1038\/srep38305 (2016).","journal-title":"Sci Rep"},{"key":"50595_CR18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nchembio.766","volume":"8","author":"R Lawrence","year":"2012","unstructured":"Lawrence, R. et al. Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses. Nat Chem Biol 8, 197\u2013204, https:\/\/doi.org\/10.1038\/nchembio.766 (2012).","journal-title":"Nat Chem Biol"},{"key":"50595_CR19","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.2307\/2531734","volume":"44","author":"SL Zeger","year":"1988","unstructured":"Zeger, S. L., Liang, K. Y. & Albert, P. S. Models for longitudinal data: a generalized estimating equation approach. Biometrics 44, 1049\u20131060 (1988).","journal-title":"Biometrics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-50595-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-50595-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-50595-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T14:10:45Z","timestamp":1671286245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-50595-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["50595"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-50595-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,1]]},"assertion":[{"value":"6 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr\u2019s Lund, Polgreen and Orchard have received research funding, consulting fees, and travel expenses from Sanofi-Genzyme. Dr. Miller is an employee of Sangamo Therapeutics. Dr\u2019s Tolar, Bigger, Liao, Shanley, Pasqali, and Ms. Sando declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"14105"}}