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Fabry disease, enzyme replacement therapy and the significance of antibody responses

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  • Published:
Journal of Inherited Metabolic Disease

Abstract

Fabry disease is an X-linked disorder caused by a deficiency of α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms – agalsidase alfa and agalsidase beta – have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain differences in post-translational modification that may affect immunogenicity. Immunoglobulin (Ig) G antibodies have frequently been reported in patients with Fabry disease receiving ERT; IgG responses are reported in a greater proportion of patients receiving agalsidase beta than in patients receiving agalsidase alfa. IgE antibodies are less common than IgG antibodies, and have not been observed in patients receiving agalsidase alfa. However, these data are difficult to interpret due to methodological differences in the assessment of seropositivity, and in the doses of enzyme used. The clinical impact of the development of IgG antibodies to ERT in patients with Fabry disease remains unclear, due to lack of data and to the marked heterogeneity of patients both in terms of disease manifestations and response to therapy. Further studies that examine the development of antibodies in patients with Fabry disease and the potential impact of such antibodies on the outcome of ERT are necessary.

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Notes

  1. 29 of the 31 patients receiving the 0.2 mg/kg biweekly dose had been part of the previous head-to head clinical trial.

References

  • Anderson W (1898) A case of angiokeratoma. Br J Dermatol 18:113–117

    Article  Google Scholar 

  • Antonelli G et al. (1996) Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-alpha2 therapy. Clin Exp Immunol 104(3):384–387

    Article  PubMed  CAS  Google Scholar 

  • Ashwell G, Harford J (1982) Carbohydrate-specific receptors of the liver. Annu Rev Biochem 51:531–554

    Article  PubMed  CAS  Google Scholar 

  • Banikazemi M et al. (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146(2):77–86

    PubMed  Google Scholar 

  • Barbey F et al. (2004) Efficacy of enzyme replacement therapy in Fabry disease. Curr Med Chem Cardiovasc Hematol Agents 2(4):277–286

    Article  PubMed  CAS  Google Scholar 

  • Beck M (2002) Agalsidase alfa–a preparation for enzyme replacement therapy in Anderson-Fabry disease. Expert Opin Investig Drugs 11(6):851–858

    Article  PubMed  CAS  Google Scholar 

  • Bekri S (2006) Importance of glycosylation in enzyme replacement therapy, in Fabry disease: perspectives from 5 years of FOS. In: Mehta A, Beck M, and Sunderplassmann G (Eds), Oxford: Oxford PharmaGenesis Ltd. pp 45–50

  • Bekri S et al. (2005) Fabry disease in patients with end-stage renal failure: the potential benefits of screening. Nephron Clin Pract 101(1):c33–c38

    Article  PubMed  Google Scholar 

  • Bekri S et al. (2006) The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of the efficacy of treatment of Fabry disease: a review of the literature. Cardiovasc Hematol Agents Med Chem 4(4):289–297

    Article  PubMed  CAS  Google Scholar 

  • Bénichou B et al. (2009) A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab 96(1):4–12

    Article  PubMed  CAS  Google Scholar 

  • Blom D et al. (2003) Recombinant enzyme therapy for Fabry disease: absence of editing of human alpha-galactosidase A mRNA. Am J Hum Genet 72(1):23–31

    Article  PubMed  CAS  Google Scholar 

  • Bodensteiner D et al. (2008) Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme. Genet Med 10(5):353–358

    Article  PubMed  CAS  Google Scholar 

  • Brady RO et al. (1967) Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med 276(21):1163–1167

    Article  PubMed  CAS  Google Scholar 

  • Branton MH et al. (2002) Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore) 81(2):122–138

    Article  CAS  Google Scholar 

  • Brooks SA (2004) Appropriate glycosylation of recombinant proteins for human use: implications of choice of expression system. Mol Biotechnol 28(3):241–255

    Article  PubMed  CAS  Google Scholar 

  • Brouns R et al. (2007) Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke. Clin Neurol Neurosurg 109(6):479–484

    Article  PubMed  Google Scholar 

  • Casadevall N et al. (2002) Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 346(7):469–475

    Article  PubMed  CAS  Google Scholar 

  • Chimenti C et al. (2004) Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation 110(9):1047–1053

    Article  PubMed  CAS  Google Scholar 

  • Chou HH et al. (2002) Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci U S A 99(18):11736–11741

    Article  PubMed  CAS  Google Scholar 

  • Christensen EI (2002) Pathophysiology of protein and vitamin handling in the proximal tubule. Nephrol Dial Transplant 17(Suppl 9):57–58

    Article  PubMed  CAS  Google Scholar 

  • Christensen EI et al. (2007) Distribution of alpha-galactosidase A in normal human kidney and renal accumulation and distribution of recombinant alpha-galactosidase A in Fabry mice. J Am Soc Nephrol 18(3):698–706

    Article  PubMed  CAS  Google Scholar 

  • Clark AT et al. (2009) Successful oral tolerance induction in severe peanut allergy. Allergy 64(8):1218–1220

    Article  PubMed  CAS  Google Scholar 

  • Clarke JT et al. (2007) The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease. Genet Med 9(8):504–509

    Article  PubMed  CAS  Google Scholar 

  • Desnick RJ, Ioannou YA, Eng CM (1995) A-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. 7th ed. Vol. 2. McGraw-Hill, New York, pp 2741–2784

    Google Scholar 

  • Eng CM et al. (2001a) Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 345(1):9–16

    Article  PubMed  CAS  Google Scholar 

  • Eng CM et al. (2001b) A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 68(3):711–722

    Article  PubMed  CAS  Google Scholar 

  • Fabry J (1898) Ein Beitrag zur Kenntnis der Purpura haemorrhagica nodularis (Purpura papulosa haemorrhagica Hebrae). Arch Dermatol Syph 43:187–200

    Article  Google Scholar 

  • Fineberg SE et al. (1983) Immunogenicity of recombinant DNA human insulin. Diabetologia 25(6):465–469

    Article  PubMed  CAS  Google Scholar 

  • Galili U et al. (1996) Enhancement of antigen presentation of influenza virus hemagglutinin by the natural human anti-Gal antibody. Vaccine 14(4):321–328

    Article  PubMed  CAS  Google Scholar 

  • Garman SC, Garboczi DN (2004) The molecular defect leading to Fabry disease: structure of human a-galactosidase. J Mol Biol 337(2):319–335

    Article  PubMed  CAS  Google Scholar 

  • Germain DP et al. (2007) Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 18(5):1547–1557

    Article  PubMed  CAS  Google Scholar 

  • Ghaderi D et al. (2010) Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol 28(8):863–867

    Article  PubMed  CAS  Google Scholar 

  • Giannelli G et al. (1994) Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN-alpha) during therapy for chronic hepatitis C. Clin Exp Immunol 97(1):4–9

    Article  PubMed  CAS  Google Scholar 

  • Gold KF et al. (2002) Quality of life of patients with Fabry disease. Qual Life Res 11(4):317–327

    Article  PubMed  CAS  Google Scholar 

  • Gribben JG et al. (1990) Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 335(8687):434–437

    Article  PubMed  CAS  Google Scholar 

  • Gupta S et al. (2005) The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 84(5):261–268

    Article  CAS  Google Scholar 

  • Hoffmann B et al. (2007) Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy - a retrospective analysis from the Fabry Outcome Survey. Clin J Pain 23(6):535–542

    Article  PubMed  Google Scholar 

  • Howard JG, Mitchison NA (1975) Immunological tolerance. Prog Allergy 18:43–96

    PubMed  CAS  Google Scholar 

  • Huby RD, Dearman RJ, Kimber I (2000) Why are some proteins allergens? Toxicol Sci 55(2):235–246

    Article  PubMed  CAS  Google Scholar 

  • Hughes DA et al. (2008) Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 94(2):153–158

    Article  PubMed  CAS  Google Scholar 

  • Hunt SV (2009) Perspectives from B cellimmunology: fact and fancy

  • Ioannou YA et al. (1998) Human a-galactosidase A: glycosylation site 3 is essential for enzyme solubility. Biochem J 332(Pt 3):789–797

    PubMed  CAS  Google Scholar 

  • Jenkins N, Parekh RB, James DC (1996) Getting the glycosylation right: implications for the biotechnology industry. Nat Biotechnol 14(8):975–981

    Article  PubMed  CAS  Google Scholar 

  • Kakkis E et al. (2004) Successful induction of immune tolerance to enzyme replacement therapy in canine mucopolysaccharidosis I. Proc Natl Acad Sci U S A 101(3):829–834

    Article  PubMed  CAS  Google Scholar 

  • Keating GM, Simpson D (2007) Agalsidase Beta: a review of its use in the management of Fabry disease. Drugs 67(3):435–455

    Article  PubMed  CAS  Google Scholar 

  • Kishnani PS et al. (2010) Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab 99(1):26–33

    Article  PubMed  CAS  Google Scholar 

  • Kleinert J et al. (2009) Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria. Transpl Int 22(3):287–292

    Article  PubMed  Google Scholar 

  • Lee K et al. (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 13(4):305–313

    Article  PubMed  Google Scholar 

  • Linhart A, Elliott PM (2007) The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart 93(4):528–535

    Article  PubMed  Google Scholar 

  • Linthorst GE et al. (2003) alpha-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease. Nephrol Dial Transplant 18(8):1581–1584

    Article  PubMed  CAS  Google Scholar 

  • Linthorst GE et al. (2004) Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 66(4):1589–1595

    Article  PubMed  CAS  Google Scholar 

  • Linthorst GE et al. (2010) Screening for Fabry disease in high-risk populations: a systematic review. J Med Genet 47(4):217–222

    Article  PubMed  CAS  Google Scholar 

  • Lubanda JC et al. (2009) Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 11(4):256–264

    Article  PubMed  CAS  Google Scholar 

  • Lusher JM (2000) Inhibitor antibodies to factor VIII and factor IX: management. Semin Thromb Hemost 26(2):179–188

    Article  PubMed  CAS  Google Scholar 

  • MacDermot KD, Holmes A, Miners AH (2001a) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38(11):769–775

    Article  PubMed  CAS  Google Scholar 

  • MacDermot KD, Holmes A, Miners AH (2001b) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38(11):750–760

    Article  PubMed  CAS  Google Scholar 

  • Matsuura F et al. (1998) Human alpha-galactosidase A: characterization of the N-linked oligosaccharides on the intracellular and secreted glycoforms overexpressed by Chinese hamster ovary cells. Glycobiology 8(4):329–339

    Article  PubMed  CAS  Google Scholar 

  • Meager A (1994) Human antibodies to insulin in diabetes. J Interferon Res 14(4):181–182

    Article  PubMed  CAS  Google Scholar 

  • Mehta A, Hughes DA (2008) Anderson-Fabry disease. alpha-galactosidase A deficiency. Includes: classic Fabry disease, atypical variants of Fabry disease. GeneReviews

  • Mehta A et al. (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34(3):236–242

    Article  PubMed  CAS  Google Scholar 

  • Mehta A et al. (2008) Enzyme replacement therapy in Fabry disease: comparison of agalsidase alfa and agalsidase beta. Mol Genet Metab 95(1–2):114–115

    Article  PubMed  CAS  Google Scholar 

  • Meikle PJ et al. (1999) Prevalence of lysosomal storage disorders. JAMA 281(3):249–254

    Article  PubMed  CAS  Google Scholar 

  • Mills K et al. (2004) Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease. Eur J Pediatr 163(10):595–603

    PubMed  CAS  Google Scholar 

  • Nalivaeva NN, Turner AJ (2001) Post-translational modifications of proteins: acetylcholinesterase as a model system. Proteomics 1(6):735–747

    Article  PubMed  CAS  Google Scholar 

  • Noguchi A et al. (1995) Immunogenicity of N-glycolylneuraminic acid-containing carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. J Biochem 117(1):59–62

    PubMed  CAS  Google Scholar 

  • Ohashi T et al. (2007) Influence of antibody formation on reduction of globotriaosylceramide (GL-3) in urine from Fabry patients during agalsidase beta therapy. Mol Genet Metab 92(3):271–273

    Article  PubMed  CAS  Google Scholar 

  • Ohashi T et al. (2008) Reduced alpha-Gal A enzyme activity in Fabry fibroblast cells and Fabry mice tissues induced by serum from antibody positive patients with Fabry disease. Mol Genet Metab 94(3):313–318

    Article  PubMed  CAS  Google Scholar 

  • Passini MA et al. (2007) Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse. Proc Natl Acad Sci U S A 104(22):9505–9510

    Article  PubMed  CAS  Google Scholar 

  • Pastores GM et al. (2007) Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 22(7):1920–1925

    Article  PubMed  CAS  Google Scholar 

  • Pinto R et al. (2004) Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 12(2):87–92

    Article  PubMed  Google Scholar 

  • Poorthuis BJ et al. (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105(1–2):151–156

    PubMed  CAS  Google Scholar 

  • Porter S (2001) Human immune response to recombinant human proteins. J Pharm Sci 90(1):1–11

    Article  PubMed  CAS  Google Scholar 

  • Prabhakar SS, Muhlfelder T (1997) Antibodies to recombinant human erythropoietin causing pure red cell aplasia. Clin Nephrol 47(5):331–335

    PubMed  CAS  Google Scholar 

  • Quesada JR et al. (1985) Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol 3(11):1522–1528

    PubMed  CAS  Google Scholar 

  • Richards SM (2002) Immunologic considerations for enzyme replacement therapy in the treatment of lysosomal storage disorders. Clin Applied Immunol Rev 2:241–253

    Article  CAS  Google Scholar 

  • Richards SM, Olson TA, McPherson JM (1993) Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. Blood 82(5):1402–1409

    PubMed  CAS  Google Scholar 

  • Ries M et al. (2006) Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 118(3):924–932

    Article  PubMed  Google Scholar 

  • Ries M et al. (2007) Enzyme replacement in Fabry disease: pharmacokinetics and pharmacodynamics of agalsidase alpha in children and adolescents. J Clin Pharmacol 47(10):1222–1230

    Article  PubMed  CAS  Google Scholar 

  • Rolfs A et al. (2005) Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 366(9499):1794–1796

    Article  PubMed  Google Scholar 

  • Rosenberg M et al. (1999) Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction of humoral tolerance in seroconverted patients after repeat administration. Blood 93(6):2081–2088

    PubMed  CAS  Google Scholar 

  • Rossman HS (2004) Neutralizing antibodies to multiple sclerosis treatments. J Manag Care Pharm 10(3 Suppl B):S12–S19

    PubMed  Google Scholar 

  • Sakuraba H et al. (2006) Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. J Hum Genet 51(3):180–188

    Article  PubMed  CAS  Google Scholar 

  • Schellekens H (2002) Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 24(11):1720–1740

    Article  PubMed  CAS  Google Scholar 

  • Schellekens H (2003) Immunogenicity of therapeutic proteins. Nephrol Dial Transplant 18(7):1257–1259

    Article  PubMed  CAS  Google Scholar 

  • Schellekens H (2005) Factors influencing the immunogenicity of therapeutic proteins. Nephrol Dial Transplant 20(Suppl 6):vi3–vi9

    Article  PubMed  CAS  Google Scholar 

  • Schellekens H (2008) The immunogenicity of therapeutic proteins and the Fabry antibody standardization initiative. Clin Ther 30:50–51

    Article  Google Scholar 

  • Schellekens H, Casadevall N (2004) Immunogenicity of recombinant human proteins: causes and consequences. J Neurol 251(Suppl 2):II4–II9

    PubMed  Google Scholar 

  • Schiffmann R et al. (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285(21):2743–2749

    Article  PubMed  CAS  Google Scholar 

  • Schiffmann R et al. (2006) Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 21(2):345–354

    Article  PubMed  CAS  Google Scholar 

  • Schiffmann R et al. (2007) Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol 18(5):1576–1583

    Article  PubMed  CAS  Google Scholar 

  • Sharma B (2007) Immunogenicity of therapeutic proteins. Part 3: impact of manufacturing changes. Biotechnol Adv 25(3):325–331

    Article  PubMed  CAS  Google Scholar 

  • Sirrs S, et al. (2009) Baseline characteristics of patients enrolled in the Canadian Fabry Disease Initiative. Mol Genet Metab

  • Sorensen PS et al. (2005) Appearance and disappearance of neutralizing antibodies during interferon-beta therapy. Neurology 65(1):33–39

    Article  PubMed  CAS  Google Scholar 

  • Spada M et al. (2006) High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 79(1):31–40

    Article  PubMed  CAS  Google Scholar 

  • Sun B et al. (2007) Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance. Am J Hum Genet 81(5):1042–1049

    Article  PubMed  CAS  Google Scholar 

  • Thurberg BL et al. (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62(6):1933–1946

    Article  PubMed  CAS  Google Scholar 

  • van Breemen MJ et al. (2011) Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy. Biochim Biophys Acta 1812(1):70–76

    PubMed  Google Scholar 

  • Vedder AC et al. (2007a) The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 30(1):68–78

    Article  PubMed  CAS  Google Scholar 

  • Vedder AC et al. (2007b) Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS One 2(7):e598

    Article  PubMed  Google Scholar 

  • Vedder AC et al. (2008) Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3. Mol Genet Metab 94(3):319–325

    Article  PubMed  CAS  Google Scholar 

  • Waldek S et al. (2009) Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med 11(11):790–796

    Article  PubMed  Google Scholar 

  • Wang J et al. (2008) Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat Biotechnol 26(8):901–908

    Article  PubMed  CAS  Google Scholar 

  • Whitfield PD et al. (2005) Monitoring enzyme replacement therapy in Fabry disease - role of urine globotriaosylceramide. J Inherit Metab Dis 28(1):21–33

    Article  PubMed  CAS  Google Scholar 

  • Whybra C et al. (2009) A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med 11(6):441–449

    Article  PubMed  CAS  Google Scholar 

  • Wight J, Paisley S, Knight C (2003) Immune tolerance induction in patients with haemophilia A with inhibitors: a systematic review. Haemophilia 9(4):436–463

    Article  PubMed  CAS  Google Scholar 

  • Wilcox WR et al. (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75(1):65–74

    Article  PubMed  CAS  Google Scholar 

  • Wraith JE, et al. (2008) Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr 152(4): 563–70, 570 e1

    Google Scholar 

  • Young E et al. (2005) Is globotriaosylceramide a useful biomarker in Fabry disease? Acta Paediatr Suppl 94(447):51–54, discussion 37–8

    Article  PubMed  CAS  Google Scholar 

  • Zhu A, Hurst R (2002) Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation 9(6):376–381

    Article  PubMed  Google Scholar 

  • Ziegler RJ et al. (2007) Correction of the biochemical and functional deficits in fabry mice following AAV8-mediated hepatic expression of alpha-galactosidase A. Mol Ther 15(3):492–500

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The author would like to thank Dr Rainer Döffinger for his advice regarding immunological perspectives.

Medical writing support to the author during the preparation of the manuscript was provided by Harriet Crofts, PhD, of Oxford PharmaGenesis Ltd and was sponsored by Shire Human Genetic Therapies, Inc. (Shire HGT). The sponsor had no influence on the contents or direction of the manuscript. The author takes full responsibility for the content of the paper.

Conflict of interest

Dr Patrick Deegan has been an investigator in clinical trials sponsored by Shire, Genzyme, Actelion, Protalix and Amicus and has received travel support for meeting attendance from each company. He has also received laboratory research grants from Shire and Genzyme and speaker honoraria from Shire, Genzyme and Actelion.

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    Patrick B. Deegan

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Deegan, P.B. Fabry disease, enzyme replacement therapy and the significance of antibody responses. J Inherit Metab Dis 35, 227–243 (2012). https://doi.org/10.1007/s10545-011-9400-y

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