{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:24:36Z","timestamp":1770351876402,"version":"3.49.0"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Energy and Industrial Technology Development Organization","award":["15664153"],"award-info":[{"award-number":["15664153"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Current therapies for the mucopolysaccharidoses (MPS) do not effectively address skeletal and neurological manifestations. Pentosan polysulfate (PPS) is an alternative treatment strategy that has been shown to improve bone architecture, mobility, and neuroinflammation in MPS animals. The aims of this study were to a) primarily establish the safety of weekly PPS injections in attenuated MPS II, b) assess the efficacy of treatment on MPS pathology, and c) define appropriate clinical endpoints and biomarkers for future clinical trials. Subcutaneous injections were administered to three male Japanese patients for 12 weeks. Enzyme replacement therapy was continued in two of the patients while they received PPS and halted for two months in one patient before starting PPS. During treatment, one patient experienced an elevation of alanine transaminase, and another patient experienced convulsions; however, these incidences were non-cumulative and unrelated to PPS administration, respectively. Overall, the drug was well-tolerated in all patients, and no serious drug-related adverse events were noted. Generally, PPS treatment led to an increase in several parameters of shoulder range of motion and decrease of the inflammatory cytokines, MIF and TNF-\u03b1, which are potential clinical endpoints and biomarkers, respectively. Changes in urine and serum glycosaminoglycans were inconclusive. Overall, this study demonstrates the safety of using PPS in adults with MPS II and suggests the efficacy of PPS on MPS pathology with the identification of potential clinical endpoints and biomarkers.<\/jats:p>","DOI":"10.3390\/diagnostics9040226","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety Study of Sodium Pentosan Polysulfate for Adult Patients with Mucopolysaccharidosis Type II"],"prefix":"10.3390","volume":"9","author":[{"given":"Kenji","family":"Orii","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaena","family":"Lim","sequence":"additional","affiliation":[{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-2834","authenticated-orcid":false,"given":"Yasuyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Medical Education Development Center, Gifu University, Gifu 501-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Calogera M.","family":"Simonaro","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward H.","family":"Schuchman","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Fukao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"ReqMed Company, Ltd., Tokyo 194-0022, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1136\/adc.72.3.263","article-title":"The mucopolysaccharidoses: A clinical review and guide to management","volume":"72","author":"Wraith","year":"1995","journal-title":"Arch. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Applegarth, D.A., Toone, J.R., and Lowry, R.B. (2000). Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics.","DOI":"10.1542\/peds.105.1.e10"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s10545-005-0112-z","article-title":"Cumulative incidence rates of the mucopolysaccharidoses in Germany","volume":"28","author":"Baehner","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.281.3.249","article-title":"Prevalence of lysosomal storage disorders","volume":"281","author":"Meikle","year":"1999","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s004390050641","article-title":"Incidence of the mucopolysaccharidoses in Northern Ireland","volume":"101","author":"Nelson","year":"1997","journal-title":"Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ajmg.a.20314","article-title":"Incidence of the mucopolysaccharidoses in Western Australia","volume":"123A","author":"Nelson","year":"2003","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s004399900075","article-title":"The frequency of lysosomal storage diseases in The Netherlands","volume":"105","author":"Poorthuis","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/ajmg.a.32781","article-title":"Incidence of the mucopolysaccharidoses in Taiwan","volume":"149A","author":"Lin","year":"2009","journal-title":"Am. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1750-1172-5-14","article-title":"Expression of the disease on female carriers of X-linked lysosomal disorders: A brief review","volume":"28","author":"Pinto","year":"2010","journal-title":"OrphanetJ. Rare. Dis."},{"key":"ref_10","unstructured":"Scriver, C.R., Baudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W., and Vogelstein, B. (2001). The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease, McGrawHill. [8th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1542\/peds.2007-1350","article-title":"Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome)","volume":"121","author":"Martin","year":"2008","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Santos, J.I., and Alves, S. (2016). Less is more: Substrate reduction therapy for lysosomal storage disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071065"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1542\/peds.2006-2156","article-title":"Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: Results of a multinational study of recombinant human \u03b1-L-iduronidase (laronidase)","volume":"120","author":"Wraith","year":"2007","journal-title":"Pediatrics."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jpeds.2004.01.046","article-title":"Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase)","volume":"144","author":"Wraith","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1203\/PDR.0b013e3181b24e94","article-title":"Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease","volume":"66","author":"Kishnani","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s10545-011-9400-y","article-title":"Fabry disease, enzyme replacement therapy and the significance of antibody responses","volume":"35","author":"Deegan","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/gim.2013.154","article-title":"A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: Safety and tolerability","volume":"16","author":"Pastores","year":"2014","journal-title":"Genet. Med."},{"key":"ref_18","first-page":"215","article-title":"Current and potential therapeutic strategies for mucopolysaccharidoses","volume":"39","author":"Noh","year":"2014","journal-title":"J. Clin. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0022-3476(98)70201-X","article-title":"Follow-up of nine patients with Hurler syndrome after bone marrow transplantation","volume":"133","author":"Guffon","year":"1998","journal-title":"J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1056\/NEJM198412203112504","article-title":"Bone-marrow transplantation in the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI)","volume":"311","author":"Krivit","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1053\/j.seminhematol.2009.10.008","article-title":"Transplant outcomes in mucopolysaccharidoses seminars in hematology","volume":"47","author":"Prasad","year":"2010","journal-title":"Semin. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/sj.bmt.1704105","article-title":"Outcome of 27 patients with Hurler\u2019s syndrome transplanted from either related or unrelated haematopoietic stem cell sources","volume":"13","author":"Souillet","year":"2003","journal-title":"Bone Marrow Transpl."},{"key":"ref_23","first-page":"62","article-title":"Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up","volume":"12","author":"Barth","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10545-005-0258-8","article-title":"Trends in haematopoietic cell transplantation for inborn errors of metabolism","volume":"29","author":"Boelens","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_25","first-page":"31","article-title":"Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA","volume":"1","author":"Chinen","year":"2014","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.bbmt.2017.06.020","article-title":"Hematopoetic stem cell transplantation for patients with mucopolysaccharidosis II","volume":"23","author":"Kubaski","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbmt.2005.09.016","article-title":"Results of the cord blood transplantation study (COBLT): Outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases","volume":"12","author":"Martin","year":"2006","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ymgme.2010.09.010","article-title":"Clinical outcomes following hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis VI","volume":"102","author":"Turbeville","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.bbmt.2016.08.015","article-title":"Allogeneic hematopoietic stem cell transplantation in thirty-four pediatric cases of mucopolysaccharidosis- a ten year report from the China Children Transplant Group","volume":"22","author":"Wang","year":"2016","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ymgme.2015.09.011","article-title":"Hematopoietic stem cell transplantation for Morquio A syndrome","volume":"117","author":"Yabe","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/sj.bmt.1701141","article-title":"Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation","volume":"21","author":"Yamada","year":"1998","journal-title":"Blood Marrow Transpl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ymgme.2014.12.001","article-title":"Therapies for the bone in mucopolysaccharidoses","volume":"114","author":"Tomatsu","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ymgme.2014.11.002","article-title":"Activities of daily living in patients with Hunter syndrome: Impact of enzyme replacement therapy and hematopoietic stem cell transplantation","volume":"114","author":"Tanjuakio","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1182\/blood-2014-11-608075","article-title":"Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: An international multicenter study","volume":"125","author":"Aldenhoven","year":"2015","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/petr.12109","article-title":"Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: A report from the Australian and New Zealand Children\u2019s Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry","volume":"17","author":"Mitchell","year":"2013","journal-title":"Pediatr. Transpl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1023\/A:1005525931994","article-title":"Long-term follow-up following bone marrow transplantation for Hunter disease","volume":"22","author":"Vellodi","year":"1999","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/8904_2012_175","article-title":"Prevalence and development of orthopaedic symptoms in the dutch hurler patient population after haematopoietic stem cell transplantation","volume":"9","author":"Stoop","year":"2013","journal-title":"Jimd Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/BPO.0b013e3181649e25","article-title":"Mobility in Hurler syndrome","volume":"28","author":"Taylor","year":"2008","journal-title":"J. Pediatr. Orthop."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/1750-1172-8-155","article-title":"Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: Results of an international consensus procedure","volume":"3","author":"Langereis","year":"2013","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1097\/01241398-199611000-00006","article-title":"Hip dysplasia in Hurler\u2019s syndrome: Orthopaedic management after bone marrow transplantation","volume":"16","author":"Masterson","year":"1996","journal-title":"J. Pediatr. Orthop."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1476-5381.2009.00565.x","article-title":"Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II","volume":"159","author":"Friso","year":"2010","journal-title":"Br. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ymgme.2009.06.013","article-title":"Genistein reduces lysosomal storage in peripheral tissues of mucopolysaccharide IIB mice","volume":"98","author":"Malinowska","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0094-0143(21)00597-8","article-title":"The therapeutic role of sulfated polysaccharides in the urinary bladder","volume":"21","author":"Parsons","year":"1994","journal-title":"Urol. Clin. North. Am."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0022-5347(05)64909-9","article-title":"Sodium pentosan polysulfate reduces urothelial responses to inflammatory stimuli via an indirect mechanism","volume":"168","author":"Sadhukhan","year":"2002","journal-title":"J. Urol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1016\/S0022-5347(05)66981-9","article-title":"Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: An alternative explanation of its beneficial effect in interstitial cystitis","volume":"164","author":"Chiang","year":"2002","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1751-0813.2012.00959.x","article-title":"Effects of intra-articular sodium pentosan polysulfate and glucosamine on the cytology, total protein concentration and viscosity of synovial fluid in horses","volume":"90","author":"Kwan","year":"2012","journal-title":"Aust. Vet. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1016\/j.febslet.2008.07.036","article-title":"Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes","volume":"582","author":"Takizawa","year":"2008","journal-title":"Febs Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.bbadis.2015.02.004","article-title":"Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy","volume":"1852","author":"Donida","year":"2015","journal-title":"Bba- Mol. Basis Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1073\/pnas.0912937107","article-title":"Involvement of the toll-like receptor 4 pathway and use of TNF-\u03b1 antagonists for treatment of the mucopolysaccharidoses","volume":"107","author":"Simonaro","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2353\/ajpath.2008.070564","article-title":"Mechanism of glycosaminoglycan-mediated bone and joint disease: Implications for the mucopolysaccharidoses and other connective tissue diseases","volume":"172","author":"Simonaro","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1203\/01.PDR.0000156510.96253.5A","article-title":"Joint and bone disease in mucopolysaccharidoses VI and VII: Identification of new therapeutic targets and biomarkers using animal models","volume":"57","author":"Simonaro","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Frohbergh, M., Ge, Y., Meng, F., Karabul, N., Solyom, A., Lai, A., Iatridis, J., Schuchman, E.H., and Simonaro, C.M. (2014). Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis Type VI rats and comparison to oral treatment. PLoS ONE.","DOI":"10.1371\/journal.pone.0100882"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Schuchman, E.H., Ge, Y., Lai, A., Borisov, Y., Faillace, M., Eliyahu, E., He, X., Iatridis, J., Vlassara, H., and Striker, G. (2013). Pentosan polysulfate: A novel therapy for mucopolysaccharidoses. PLoS ONE.","DOI":"10.1371\/journal.pone.0054459"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Simonaro, C.M., Tomatsu, S., Sikora, T., Kubaski, F., Frohbergh, M., Guevara, J.M., Wang, R.Y., Vera, M., Kang, J.L., and Smith, L.J. (2016). Pentosan polysulfate: Oral versus subcutaneous injection in mucopolysaccharidosis Type I dogs. PLoS ONE.","DOI":"10.1371\/journal.pone.0153136"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Crivaro, A.N., Mucci, J.M., Bondar, C.M., Ormazabal, M.E., Ceci, R., Simonaro, C., and Rozenfeld, P.A. (2019). Efficacy of pentosan polysulfate in in vitro models of lysosomal storage disorders: Fabry and Gaucher Disease. PLoS ONE.","DOI":"10.1371\/journal.pone.0217780"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Guo, N., DeAngelis, V., Zhu, C., Schuchman, E.H., and Simonaro, C.M. (2019). Pentosan polysulfate treatment of mucopolysaccharidosis Type IIIA mice. Jimd Rep.","DOI":"10.1007\/8904_2018_96"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s10545-016-9974-5","article-title":"Treatment with pentosan polysulphate in patients with MPS I: Results from an open label, randomized, monocentric phase II study","volume":"39","author":"Hennermann","year":"2016","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ab.2007.05.016","article-title":"Analytical method for the determination of disaccharides derived from keratan, heparan, and dermatan sulfates in human serum and plasma by high-performance liquid chromatography\/turbo ionspray ionization tandem mass spectrometry","volume":"368","author":"Oguma","year":"2007","journal-title":"Anal. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/bmc.760","article-title":"Analytical method for determination of disaccharides derived from keratan sulfates in human serum and plasma by high-performance liquid chromatography\/turbo-ionspray ionization tandem mass spectrometry","volume":"21","author":"Oguma","year":"2007","journal-title":"Biomed. Chromatogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ymgme.2009.10.001","article-title":"Validation of disaccharide compositions derived from dermatan sulfate and heparan sulfate in mucopolysaccharidoses and mucolipidoses II and III by tandem mass spectrometry","volume":"99","author":"Tomatsu","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10545-012-9522-x","article-title":"Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I., IIIA, IVA, and VII","volume":"36","author":"Rowan","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10545-009-9013-x","article-title":"Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography\u2013tandem mass spectrometry","volume":"33","author":"Tomatsu","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4137\/BMI.S7451","article-title":"Comparison of liquid chromatography\u2013tandem mass spectrometry and sandwich ELISA for determination of keratan sulfate in plasma and urine","volume":"6","author":"Hintze","year":"2011","journal-title":"Biomark Insights"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ymgme.2018.04.011","article-title":"Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis","volume":"125","author":"Shaukat","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s10545-009-1204-y","article-title":"Retinitis pigmentosa and mucopolysaccharidosis type II: An extremely attenuated phenotype","volume":"32","author":"Suzuki","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1023\/A:1005363414792","article-title":"Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II (Hunter disease)","volume":"21","author":"Isogai","year":"1998","journal-title":"J. Inher. Metab. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10038-005-0266-4","article-title":"Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II","volume":"50","author":"Kato","year":"2005","journal-title":"J. Hum. Genet."},{"key":"ref_68","first-page":"133","article-title":"Mucopolysaccharidosis type II: Idenfication of 30 novel mutations among Latin American Patients","volume":"111","author":"Schwarts","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1001\/archsurg.1976.01360190039006","article-title":"Drug prevention of postoperative deep vein thrombosiss. A comparative study of calcium heparinate and sodium pentosan polysulfate","volume":"111","author":"Joffe","year":"1979","journal-title":"Arch. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.joca.2013.08.001","article-title":"Osteoimmunology in mucopolysaccharidoses type I., II, VI and VII. Immunological regulation of the osteoarticular system in the courof metabolic inflammation","volume":"21","author":"Jurecka","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","article-title":"Cytokines, inflammation and pain","volume":"45","author":"Zhang","year":"2009","journal-title":"Int. Anesth. Clin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ymgme.2007.06.016","article-title":"Improvement in behavior after substrate deprivation therapy with rhodamine B in a mouse model of MPS IIIA","volume":"92","author":"Roberts","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Derrick-Roberts, A.L.K., Jackson, M.R., Pyragius, C.E., and Byers, S. (2017). Substrate deprivation therapy to reduce glycosaminoglycan synthesis improves aspects of neurological and skeletal pathology in MPS I mice. Diseases, 5.","DOI":"10.3390\/diseases5010005"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ymgme.2012.04.002","article-title":"Rhodamine B and 2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-D-glucopyranose (F-GlcNAc) inhibit chondroitin\/dermatan and keratan sulphate synthesis by different mechanisms in bovine chondrocytes","volume":"106","author":"Marais","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/sj.ejhg.5201623","article-title":"Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses","volume":"14","author":"Piotrowska","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Jak\u00f3bkiewicz-Banecka, J., Piotrowska, E., Narajczyk, M., Bara\u0144ska, S., and Wegrzyn, G. (2009). Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway. J. Biomed. Sci.","DOI":"10.1186\/1423-0127-16-26"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.gene.2016.03.029","article-title":"Cell cycle is disturbed in mucopolysaccharidosis type II fibroblasts, and can be improved by genistein","volume":"585","author":"Moskot","year":"2016","journal-title":"Gene"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/9\/4\/226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:43:04Z","timestamp":1760190184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/9\/4\/226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["diagnostics9040226"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics9040226","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]}}}