{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:23:35Z","timestamp":1773271415730,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T00:00:00Z","timestamp":1090540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,7,23]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Therapeutic enzymes are often recognized as foreign by the immune system of patients undergoing enzyme replacement therapy. The antibodies that develop may alter pharmacokinetics and biodistribution of the therapeutic protein, may be able to neutralize the activity of the enzyme, or may cause immune reactions in certain patients. We have explored treatment regimens to reduce the antibody response to human \u03b1-galactosidase A (r-h\u03b1GAL) in Fabry (\u03b1GAL knock-out) and normal BALB\/c mice. A wide variety of treatment modalities were tested, including high dose tolerance induction, increased frequency of therapeutic doses and immunosuppressive drugs in combination with administration of enzyme. The most substantial effects were observed in mice injected intravenously with r-h\u03b1GAL in combination with methotrexate (MTX), which significantly lowered r-h\u03b1GAL-specific serum antibody levels. A short course of treatment with MTX was able to reduce antibody and spleen cell proliferative responses to long-term r-h\u03b1GAL treatment. MTX was able to suppress the development of r-h\u03b1GAL-specific IgG in antigen-primed mice. However, MTX was not effective in dampening robust ongoing antibody responses. These experiments provide a framework for the design of clinical protocols to prevent the drug-specific antibody responses of patients undergoing enzyme replacement therapy.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02567.x","type":"journal-article","created":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T10:57:27Z","timestamp":1092999447000},"page":"496-502","source":"Crossref","is-referenced-by-count":45,"title":["Methotrexate reduces antibody responses to recombinant human<i>\u03b1<\/i>-galactosidase A therapy in a mouse model of Fabry disease"],"prefix":"10.1093","volume":"137","author":[{"given":"R D","family":"GARMAN","sequence":"first","affiliation":[{"name":"Immunology Laboratory, Cell and Protein Therapeutics R&D, Genzyme Corporation, Framingham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"MUNROE","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Cell and Protein Therapeutics R&D, Genzyme Corporation, Framingham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S M","family":"RICHARDS","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Cell and Protein Therapeutics R&D, Genzyme Corporation, Framingham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,8,9]]},"reference":[{"key":"2022011223191138200_b1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1046\/j.1365-2516.2003.00780.x","article-title":"The epidemiology of inhibitors in haemophilia A: a systematic review","volume":"9","author":"Wight","year":"2003","journal-title":"Haemophilia"},{"key":"2022011223191138200_b2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1529-1049(02)00049-1","article-title":"Immunologic considerations for enzyme replacement therapy in the treatment of lysosomal storage disorders","volume":"2","author":"Richards","year":"2002","journal-title":"Clin Appl Immunol 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