{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:53:33Z","timestamp":1793170413272,"version":"4.5.0"},"reference-count":22,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2011,1]]},"DOI":"10.1016\/j.ymgme.2010.09.004","type":"journal-article","created":{"date-parts":[[2010,9,18]],"date-time":"2010-09-18T08:51:43Z","timestamp":1284799903000},"page":"6-12","source":"Crossref","is-referenced-by-count":107,"title":["An open-label Phase I\/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay\u2013Sachs or Sandhoff variants)"],"prefix":"10.1016","volume":"102","author":[{"given":"Joe T.R.","family":"Clarke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don J.","family":"Mahuran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Sathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H.","family":"Kolodny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte A.","family":"Rigat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A.","family":"Raiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Tropak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2010.09.004_bb0005","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0925-4439(99)00074-5","article-title":"Biochemical consequences of mutations causing the GM2 gangliosidoses","volume":"1455","author":"Mahuran","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymgme.2010.09.004_bb0010","first-page":"2839","article-title":"The GM2 gangliosidoses","volume":"vol. 2","author":"Gravel","year":"1995"},{"key":"10.1016\/j.ymgme.2010.09.004_bb0015","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/BF00219337","article-title":"Quantitative correlation between the residual activity of beta-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease","volume":"88","author":"Leinekugel","year":"1992","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0020","doi-asserted-by":"crossref","first-page":"9150","DOI":"10.1074\/jbc.M609304200","article-title":"Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis","volume":"282","author":"Maegawa","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0025","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1471-4159.1988.tb13266.x","article-title":"Mutation in GM2-Gangliosidosis B1 variant","volume":"50","author":"Ohno","year":"1988","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0030","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0022-2836(03)00216-X","article-title":"Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay\u2013Sachs disease","volume":"327","author":"Mark","year":"2003","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0035","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1111\/j.1742-4658.2007.06040.x","article-title":"Lending a helping hand, screening chemical libraries for compounds that enhance \u03b2-hexosaminidase A activity in GM2 Gangliosidosis cells","volume":"274","author":"Tropak","year":"2007","journal-title":"FEBS J."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0040","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.cellbio.21.122303.120200","article-title":"Intracellular signaling by the unfolded protein response","volume":"22","author":"Bernales","year":"2006","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0045","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ymgme.2008.12.008","article-title":"Diltiazem, a L-type Ca(2+) channel blocker, also acts as a pharmacological chaperone in Gaucher patient cells","volume":"96","author":"Rigat","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0050","doi-asserted-by":"crossref","first-page":"13478","DOI":"10.1074\/jbc.M308523200","article-title":"Pharmacological enhancement of \u03b2-hexosaminidase activity in fibroblasts from adult Tay\u2013Sach and Sandhoff patients","volume":"279","author":"Tropak","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0055","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s10545-009-1077-0","article-title":"The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha-galactosidase A levels in Fabry patient cell lines","volume":"32","author":"Benjamin","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0060","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1111\/j.1742-4658.2010.07588.x","article-title":"The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase","volume":"277","author":"Khanna","year":"2010","journal-title":"FEBS J."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0065","doi-asserted-by":"crossref","first-page":"23502","DOI":"10.1074\/jbc.M109.012393","article-title":"Identification and characterization of ambroxol as an enzyme-enhancement agent for Gaucher disease","volume":"284","author":"Maegawa","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0070","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00018-005-5437-0","article-title":"Therapeutic strategies to ameliorate lysosomal storage disorders\u2013a focus on Gaucher disease","volume":"63","author":"Sawkar","year":"2006","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0075","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10545-006-0287-y","article-title":"Beta-galactosidase deficiency: an approach to chaperone therapy","volume":"29","author":"Suzuki","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0080","doi-asserted-by":"crossref","first-page":"e1550","DOI":"10.1542\/peds.2006-0588","article-title":"The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported","volume":"118","author":"Maegawa","year":"2006","journal-title":"Pediatrics"},{"key":"10.1016\/j.ymgme.2010.09.004_bb0085","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/glycob\/cwp183","article-title":"A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates","volume":"20","author":"Tropak","year":"2010","journal-title":"Glycobiology"},{"key":"10.1016\/j.ymgme.2010.09.004_bb0090","doi-asserted-by":"crossref","first-page":"21386","DOI":"10.1074\/jbc.273.33.21386","article-title":"A Pro504Ser substitution in the \u03b2-subunit of \u03b2-hexosaminidase A inhibits \u03b1-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease","volume":"273","author":"Hou","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0095","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0100","first-page":"497","article-title":"\u03b2-hexosaminidase isozymes from cells co-transfected with \u03b1 and \u03b2 cDNA constructs: Analysis of \u03b1 subunit missense mutation associated with the adult form of Tay\u2013Sachs disease","volume":"53","author":"Brown","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0105","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1128\/AAC.40.7.1623","article-title":"Plasma pyrimethamine concentrations during long-term treatment for cerebral toxoplasmosis in patients with AIDS","volume":"40","author":"Klinker","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ymgme.2010.09.004_bb0110","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1093\/infdis\/157.3.580","article-title":"Pyrimethamine concentrations in serum and cerebrospinal fluid during treatment of acute Toxoplasma encephalitis in patients with AIDS","volume":"157","author":"Weiss","year":"1988","journal-title":"J. Infect. Dis."}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719210003458?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719210003458?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T05:04:53Z","timestamp":1636520693000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096719210003458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["S1096719210003458"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2010.09.004","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2011,1]]}}}