{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:10:43Z","timestamp":1790698243942,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005053","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina","doi-asserted-by":"publisher","award":["Explore 2"],"award-info":[{"award-number":["Explore 2"]}],"id":[{"id":"10.13039\/501100005053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005053","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina","doi-asserted-by":"publisher","award":["PegLyso"],"award-info":[{"award-number":["PegLyso"]}],"id":[{"id":"10.13039\/501100005053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005053","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina","doi-asserted-by":"publisher","award":["ADVERT"],"award-info":[{"award-number":["ADVERT"]}],"id":[{"id":"10.13039\/501100005053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2017 SGR-229"],"award-info":[{"award-number":["2017 SGR-229"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fabry disease (FD) is a lysosomal storage disease caused by mutations in the gene for the \u03b1-galactosidase A (GLA) enzyme. The absence of the enzyme or its activity results in the accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in different tissues, leading to a wide range of clinical manifestations. More than 1000 natural variants have been described in the GLA gene, most of them affecting proper protein folding and enzymatic activity. Currently, FD is treated by enzyme replacement therapy (ERT) or pharmacological chaperone therapy (PCT). However, as both approaches show specific drawbacks, new strategies (such as new forms of ERT, organ\/cell transplant, substrate reduction therapy, or gene therapy) are under extensive study. In this review, we summarize GLA mutants described so far and discuss their putative application for the development of novel drugs for the treatment of FD. Unfavorable mutants with lower activities and stabilities than wild-type enzymes could serve as tools for the development of new pharmacological chaperones. On the other hand, GLA mutants showing improved enzymatic activity have been identified and produced in vitro. Such mutants could overcome several complications associated with current ERT, as lower-dose infusions of these mutants could achieve a therapeutic effect equivalent to that of the wild-type enzyme.<\/jats:p>","DOI":"10.3390\/ijms22126518","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T21:29:16Z","timestamp":1623965356000},"page":"6518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Human \u03b1-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-1915","authenticated-orcid":false,"given":"Andrea","family":"Modrego","sequence":"first","affiliation":[{"name":"Institut de Biotecnologia i de Biomedicina, Universitat Aut\u00f2noma de Barcelona, Bellaterra, 08193 Barcelona, Spain"},{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilla","family":"Amaranto","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica Ranwel Caputto, Centro de Investigaciones en Qu\u00edmica Biol\u00f3gica de C\u00f3rdoba, CONICET, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustina","family":"Godino","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica Ranwel Caputto, Centro de Investigaciones en Qu\u00edmica Biol\u00f3gica de C\u00f3rdoba, CONICET, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i de Biomedicina, Universitat Aut\u00f2noma de Barcelona, Bellaterra, 08193 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), c\/Monforte de Lemos 3\u20135, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Barra","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica Ranwel Caputto, Centro de Investigaciones en Qu\u00edmica Biol\u00f3gica de C\u00f3rdoba, CONICET, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-144X","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Corchero","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i de Biomedicina, Universitat Aut\u00f2noma de Barcelona, Bellaterra, 08193 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), c\/Monforte de Lemos 3\u20135, 28029 Madrid, Spain"},{"name":"Departament de Gen\u00e8tica i de Microbiologia, Universitat Aut\u00f2noma de Barcelona, Bellaterra, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. 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