{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T19:54:42Z","timestamp":1774036482400,"version":"3.50.1"},"reference-count":109,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of \u03b1-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that \u201cin vitro\u201d amenability may not always reflect \u201cin vivo\u201d amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.<\/jats:p>","DOI":"10.3390\/ijms22010206","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T10:33:56Z","timestamp":1609151636000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Fabry Disease Therapy: State-of-the-Art and Current Challenges"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-3403","authenticated-orcid":false,"given":"Olga","family":"Azevedo","sequence":"first","affiliation":[{"name":"Cardiology Department, Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, 4835-044 Guimar\u00e3es, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3Bs PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-6207","authenticated-orcid":false,"given":"Miguel Fernandes","family":"Gago","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3Bs PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"Neurology Department, Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, 4835-044 Guimar\u00e3es, Portugal"}]},{"given":"Gabriel","family":"Miltenberger-Miltenyi","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3Bs PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"Genetics Department, Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, 4835-044 Guimar\u00e3es, Portugal"}]},{"given":"Nuno","family":"Sousa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3Bs PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Dami\u00e3o","family":"Cunha","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3Bs PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W., and Vogelstein, B. (2001). Alpha-galactosidase A deficiency: Fabry disease. The Metabolic and Molecular Bases of Inherited Disease, McGraw Hill."},{"key":"ref_2","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. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1681\/ASN.2016090964","article-title":"Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study","volume":"28","author":"Arends","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymgme.2019.07.012","article-title":"Founder effect of Fabry disease due to p.F113L mutation: Clinical profile of a late-onset phenotype","volume":"129","author":"Azevedo","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","first-page":"100565","article-title":"Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation","volume":"22","author":"Azevedo","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/jmg.2005.036327","article-title":"Natural history of Fabry disease in females in the Fabry Outcome Survey","volume":"43","author":"Deegan","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1023\/A:1012993305223","article-title":"Anderson-Fabry disease: Clinical manifestations of disease in female heterozygotes","volume":"24","author":"Whybra","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13023-015-0296-8","article-title":"Quality of life in patients with Fabry disease: A systematic review of the literature","volume":"10","author":"Arends","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1136\/jmg.2008.065904","article-title":"Natural course of Fabry disease: Changing pattern of causes of death in FOS\u2014Fabry Outcome Survey","volume":"46","author":"Mehta","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1097\/GIM.0b013e3181bb05bb","article-title":"Life expectancy and cause of death in males and females with Fabry disease: Findings from the Fabry Registry","volume":"11","author":"Waldek","year":"2009","journal-title":"Genet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Feriozzi, S., and Hughes, D.A. (2020). New drugs for the treatment of Anderson\u2013Fabry disease. J. Nephrol., 1\u201310.","DOI":"10.1007\/s40620-020-00721-4"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/jimd.12228","article-title":"Developments in the treatment of Fabry disease","volume":"43","author":"Hollak","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/hrt.2006.104026","article-title":"Effects of enzyme replacement therapy on the cardiomyopathy of Anderson Fabry disease: A randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa","volume":"94","author":"Hughes","year":"2008","journal-title":"Heart"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1001\/jama.285.21.2743","article-title":"Enzyme Replacement Therapy in Fabry Disease","volume":"285","author":"Schiffmann","year":"2001","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/ndt\/gfi152","article-title":"Long-term therapy with agalsidase alfa for Fabry disease: Safety and effects on renal function in a home infusion setting","volume":"21","author":"Schiffmann","year":"2005","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/8904_2015_422","article-title":"Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Na\u00efve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa","volume":"23","author":"Nedd","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ymgme.2011.03.022","article-title":"Response of women with Fabry disease to enzyme replacement therapy: Comparison with men, using data from FOS\u2014the Fabry Outcome Survey","volume":"103","author":"Hughes","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13023-015-0338-2","article-title":"Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: Cardiac outcomes after 10 years\u2019 treatment","volume":"10","author":"Kampmann","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1023\/B:BOLI.0000009948.86528.72","article-title":"Hearing loss in Fabry disease: The effect of agalsidase alfa replacement therapy","volume":"26","author":"Hajioff","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_21","first-page":"87","article-title":"\u201cInterdisciplinary Study Group On Fabry Disease\u201d Inner ear involvement in Anderson-Fabry disease: Long-term follow-up during enzyme replacement therapy","volume":"30","author":"Sergi","year":"2010","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/mus.10497","article-title":"Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease","volume":"28","author":"Schiffmann","year":"2003","journal-title":"Muscle Nerve"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s10545-006-0339-3","article-title":"Improvement of sympathetic skin responses under enzyme replacement therapy in Fabry disease","volume":"29","author":"Jardim","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10545-005-0575-y","article-title":"Enzyme replacement therapy in Japanese Fabry disease patients: The results of a phase 2 bridging study","volume":"28","author":"Eto","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/GIM.0b013e3181981d82","article-title":"Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease","volume":"11","author":"Lubanda","year":"2009","journal-title":"Genet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbadis.2010.09.007","article-title":"Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy","volume":"1812","author":"Rombach","year":"2011","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/hrt.2004.054015","article-title":"Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with galactosidase A","volume":"92","author":"Elliott","year":"2005","journal-title":"Heart"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Najafian, B., T\u00f8ndel, C., Svarstad, E., Sokolovkiy, A., Smith, K., and Mauer, M. (2016). One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152812"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/jhg.2016.78","article-title":"Long-term enzyme replacement therapy for Fabry disease: Efficacy and unmet needs in cardiac and renal outcomes","volume":"61","author":"Kim","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1093\/ndt\/gfr420","article-title":"Renal outcomes of agalsidase beta treatment for Fabry disease: Role of proteinuria and timing of treatment initiation","volume":"27","author":"Warnock","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/gim.2013.53","article-title":"Analysis of left ventricular mass in untreated men and in men treated with agalsidase-\u03b2: Data from the Fabry Registry","volume":"15","author":"Germain","year":"2013","journal-title":"Genet. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ymgme.2012.05.011","article-title":"Enzyme replacement therapy improves cardiac features and severity of Fabry disease","volume":"107","author":"Motwani","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1212\/01.WNL.0000118207.84514.40","article-title":"Enzyme replacement therapy improves function of C-, A\u03b4-, and A\u03b2-nerve fibers in Fabry neuropathy","volume":"62","author":"Hilz","year":"2004","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1053\/j.ajkd.2005.03.016","article-title":"Enzyme Replacement Therapy in Fabry Disease Patients Undergoing Dialysis: Effects on Quality of Life and Organ Involvement","volume":"46","author":"Pisani","year":"2005","journal-title":"Am. J. Kidney Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1086\/318809","article-title":"A Phase 1\/2 Clinical Trial of Enzyme Replacement in Fabry Disease: Pharmacokinetic, Substrate Clearance, and Safety Studies","volume":"68","author":"Eng","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1023\/B:BOLI.0000005658.14563.77","article-title":"Enzyme replacement therapy in heterozygous females with Fabry disease: Results of a phase IIIB study","volume":"26","author":"Baehner","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/GIM.0b013e3181a23bec","article-title":"A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease","volume":"11","author":"Whybra","year":"2009","journal-title":"Genet. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2215\/CJN.03130411","article-title":"The Effectiveness of Long-Term Agalsidase Alfa Therapy in the Treatment of Fabry Nephropathy","volume":"7","author":"Feriozzi","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/GIM.0b013e3181f13a4a","article-title":"Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry","volume":"12","author":"Watt","year":"2010","journal-title":"Genet. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJM200107053450102","article-title":"Safety and Efficacy of Recombinant Human \u03b1-Galactosidase A Replacement Therapy in Fabry\u2019s Disease","volume":"345","author":"Eng","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1086\/422366","article-title":"Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease","volume":"75","author":"Wilcox","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1096\/fj.04-2375com","article-title":"A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder","volume":"19","author":"Yam","year":"2005","journal-title":"FASEB J."},{"key":"ref_43","first-page":"4179","article-title":"In vitro inhibition and intracellular enhancement of lysosomal \u03b1-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives","volume":"267","author":"Asano","year":"2000","journal-title":"JBIC J. Biol. Inorg. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"C1076","DOI":"10.1152\/ajpcell.00426.2005","article-title":"Pharmacological chaperone corrects lysosomal storage in Fabry disease caused by trafficking-incompetent variants","volume":"290","author":"Yam","year":"2006","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_45","unstructured":"(2020, November 23). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/replagal-epar-product-information_en.pdf."},{"key":"ref_46","unstructured":"(2020, November 23). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/fabrazyme-epar-product-information_en.pdf."},{"key":"ref_47","unstructured":"(2020, November 23). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/galafold-epar-product-information_en.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1056\/NEJMoa1510198","article-title":"Treatment of Fabry\u2019s Disease with the Pharmacologic Chaperone Migalastat","volume":"375","author":"Germain","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/cpt.1321","article-title":"Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year","volume":"105","author":"Gensler","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1136\/jmedgenet-2017-104826","article-title":"Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment","volume":"54","author":"Mauer","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1136\/jmedgenet-2016-104178","article-title":"Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study","volume":"54","author":"Hughes","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ymgme.2020.07.007","article-title":"Long-term efficacy and safety of migalastat treatment in Fabry disease: 30-month results from the open-label extension of the randomized, phase 3 ATTRACT study","volume":"131","author":"Hughes","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1093\/eurheartj\/ehy072","article-title":"Treatment of hypertrophic cardiomyopathy caused by cardiospecific variants of Fabry disease with chaperone therapy","volume":"39","author":"Salinger","year":"2018","journal-title":"Eur. Hear. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/cpt.1832","article-title":"Treatment of Fabry\u2019s Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)","volume":"108","author":"Lenders","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1038\/s41431-020-0677-x","article-title":"Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: Real-life data","volume":"28","author":"Riccio","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13023-018-0813-7","article-title":"Migalastat improves diarrhea in patients with Fabry disease: Clinical-biomarker correlations from the phase 3 FACETS trial","volume":"13","author":"Schiffmann","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1681\/ASN.2006080816","article-title":"Sustained, Long-Term Renal Stabilization After 54 Months of Agalsidase \u03b2 Therapy in Patients with Fabry Disease","volume":"18","author":"Germain","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s40265-019-01090-4","article-title":"Migalastat: A Review in Fabry Disease","volume":"79","author":"McCafferty","year":"2019","journal-title":"Drugs"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ymgme.2017.05.001","article-title":"Favourable effect of early versus late start of enzyme replacement therapy on plasma globotriaosylsphingo-sine levels in men with classical Fabry disease","volume":"121","author":"Arends","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/jmedgenet-2014-102797","article-title":"Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease","volume":"52","author":"Germain","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_61","first-page":"524","article-title":"Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy","volume":"119","author":"Weidemann","year":"2009","journal-title":"Cir-Culation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ymgme.2016.06.007","article-title":"Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry","volume":"119","author":"Hopkin","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7326\/0003-4819-146-2-200701160-00148","article-title":"Agalsidase-Beta Therapy for Advanced Fabry Disease","volume":"146","author":"Banikazemi","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1136\/jmedgenet-2017-104863","article-title":"Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: An international cohort study","volume":"55","author":"Arends","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ymgme.2014.01.014","article-title":"Outcomes of patients treated through the Canadian Fabry disease initiative","volume":"111","author":"Sirrs","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1750-1172-6-69","article-title":"Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients","volume":"6","author":"Smid","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/8904_2011_44","article-title":"Effect of Reduced Agalsidase Beta Dosage in Fabry Patients: The Australian Experience","volume":"3","author":"Ghali","year":"2011","journal-title":"JIMD Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1681\/ASN.2013060585","article-title":"Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch","volume":"25","author":"Weidemann","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1681\/ASN.2015030337","article-title":"Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch\u20132-Year Follow-Up","volume":"27","author":"Lenders","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_70","first-page":"807","article-title":"Reaccumulation of globotriaosylceramide in podocytes after agalsidase dose reduction in young Fabry patients","volume":"32","author":"Skrunes","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_71","first-page":"3435","article-title":"Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease","volume":"9","author":"Holida","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ymgme.2013.04.015","article-title":"A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease","volume":"109","author":"Hughes","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1681\/ASN.2006111263","article-title":"Weekly Enzyme Replacement Therapy May Slow Decline of Renal Function in Patients with Fabry Disease Who Are on Long-Term Biweekly Dosing","volume":"18","author":"Schiffmann","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s10545-015-9845-5","article-title":"A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease","volume":"38","author":"Schiffmann","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1161\/CIRCULATIONAHA.108.841494","article-title":"Cardiac Microvascular Pathology in Fabry Disease","volume":"119","author":"Thurberg","year":"2009","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1046\/j.1523-1755.2002.00675.x","article-title":"Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy","volume":"62","author":"Thurberg","year":"2002","journal-title":"Kidney Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1136\/hrt.2005.063818","article-title":"The heart in Anderson-Fabry disease and other lysosomal storage disorders","volume":"93","author":"Linhart","year":"2007","journal-title":"Heart"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s10545-012-9472-3","article-title":"Lysosomal delivery of therapeutic enzymes in cell models of Fabry disease","volume":"35","author":"Marchesan","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Prabakaran, T., Nielsen, R., Larsen, J.V., S\u00f8rensen, S.S., Rasmussen, U.F., Saleem, M.A., Petersen, C.M., Verroust, P.J., and Christensen, E.I. (2011). Receptor-Mediated Endocytosis of \u03b1-Galactosidase A in Human Podocytes in Fabry Disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025065"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ymgme.2018.08.014","article-title":"Development and clinical consequences of white matter lesions in Fabry disease: A systematic review","volume":"125","author":"Vergouwe","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1440-1789.2008.00883.x","article-title":"An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia","volume":"28","author":"Okeda","year":"2008","journal-title":"Neuropathology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00428-005-0089-x","article-title":"Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement","volume":"448","author":"Schiffmann","year":"2005","journal-title":"Virchows Archiv"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ana.410310410","article-title":"Fabry disease: Immunocytochemical characterization of neuronal involvement","volume":"31","author":"Schwarting","year":"1992","journal-title":"Ann. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1590\/S0004-282X2006000500002","article-title":"White matter lesions in Fabry disease before and after enzyme replacement therapy: A 2-year follow-up","volume":"64","author":"Jardim","year":"2006","journal-title":"Arq. Neuro-Psiquiatr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1159\/000369293","article-title":"Enzyme Replacement Therapy Stabilized White Matter Lesion Progression in Fabry Disease","volume":"38","author":"Fellgiebel","year":"2014","journal-title":"Cerebrovasc. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ymgme.2012.12.005","article-title":"A revised home treatment algorithm for Fabry disease: Influence of antibody formation","volume":"108","author":"Smid","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/8904_2011_106","article-title":"Severe Infusion Reactions to Fabry Enzyme Replacement Therapy: Rechallenge After Tracheostomy","volume":"5","author":"Nicholls","year":"2011","journal-title":"JIMD Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1681\/ASN.2014121226","article-title":"Serum-Mediated Inhibition of Enzyme Replacement Therapy in Fabry Disease","volume":"27","author":"Lenders","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1111\/j.1523-1755.2004.00924.x","article-title":"Enzyme therapy for Fabry disease: Neutralizing antibodies toward agalsidase alpha and beta","volume":"66","author":"Linthorst","year":"2004","journal-title":"Kidney Int."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1681\/ASN.2018030329","article-title":"Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with Fabry Disease","volume":"29","author":"Lenders","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Rombach, S.M., Aerts, J.M.F.G., Poorthuis, B.J.H.M., Groener, J.E.M., Donker-Koopman, W., Hendriks, E., Mirzaian, M., Kuiper, S., Wijburg, F.A., and Hollak, C.E.M. (2012). Long-Term Effect of Antibodies against Infused Alpha-Galactosidase A in Fabry Disease on Plasma and Urinary (lyso)Gb3 Reduction and Treatment Outcome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047805"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2008.10.004","article-title":"A retrospective analysis of the potential impact of IgG antibodies to agalsidase \u03b2 on efficacy during enzyme replacement therapy for Fabry disease","volume":"96","author":"Goyal","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ymgme.2018.11.008","article-title":"Antibodies against recombinant alpha-galactosidase A in Fabry disease: Subclass analysis and impact on response to treatment","volume":"126","author":"Hollak","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1681\/ASN.2018070740","article-title":"Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry Disease","volume":"29","author":"Lenders","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1038\/s41436-019-0451-z","article-title":"Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: Data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study","volume":"21","author":"Germain","year":"2019","journal-title":"Genet. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/gim.2016.122","article-title":"The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat","volume":"19","author":"Benjamin","year":"2017","journal-title":"Genet. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1136\/jmedgenet-2019-106005","article-title":"Mutation-specific Fabry disease patient-derived cell model to evaluate the amenability to chaperone therapy","volume":"56","author":"Lenders","year":"2019","journal-title":"J. Med Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.omtm.2020.08.012","article-title":"In Vitro and In Vivo Amenability to Migalastat in Fabry Disease","volume":"19","author":"Lenders","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/mt.2009.220","article-title":"The Pharmacological Chaperone 1-Deoxygalactonojirimycin Reduces Tissue Globotriaosylceramide Levels in a Mouse Model of Fabry Disease","volume":"18","author":"Khanna","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ymgme.2014.08.002","article-title":"Characterization of a chemically modified plant cell culture expressed human \u03b1-Galactosidase-A enzyme for treatment of Fabry disease","volume":"114","author":"Kizhner","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/jimd.12080","article-title":"Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1\/2 clinical trial","volume":"42","author":"Schiffmann","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.ymgme.2018.12.176","article-title":"Once every 4 weeks\u20142 mg\/kg of pegunigalsidase alfa for treating Fabry disease Preliminary results of a phase 3 study","volume":"126","author":"Holida","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/j.ymgme.2018.12.234","article-title":"Pegunigalsidase alfa for the treatment of Fabry disease: Preliminary results from a phase III open label, switch over study from agalsidase alfa","volume":"126","author":"Linhart","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10545-015-9886-9","article-title":"Mannose receptor-mediated delivery of moss-made \u03b1-galactosidase A efficiently corrects enzyme deficiency in Fabry mice","volume":"39","author":"Shen","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/jimd.12052","article-title":"Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease","volume":"42","author":"Hennermann","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2119\/molmed.2015.00088","article-title":"Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease","volume":"21","author":"Ashe","year":"2015","journal-title":"Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.ymthe.2019.03.001","article-title":"Improved Efficacy in a Fabry Disease Model Using a Systemic mRNA Liver Depot System as Compared to Enzyme Replacement Therapy","volume":"27","author":"DeRosa","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.ajhg.2019.02.003","article-title":"Systemic mRNA Therapy for the Treatment of Fabry Disease: Preclinical Studies in Wild-Type Mice, Fabry Mouse Model, and Wild-Type Non-human Primates","volume":"104","author":"Zhu","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/cpt.790","article-title":"Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability, Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme Replacement","volume":"103","author":"Oder","year":"2018","journal-title":"Clin. Pharmacol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:52Z","timestamp":1760179612000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,28]]},"references-count":109,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22010206"],"URL":"https:\/\/doi.org\/10.3390\/ijms22010206","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,28]]}}}