Advertisement

Journal of Inherited Metabolic Disease

, Volume 35, Issue 2, pp 227–243 | Cite as

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

  • Patrick B. Deegan
Review

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.

Keywords

Enzyme Replacement Therapy Fabry Disease Gauche Disease Antibody Formation Lysosomal Storage Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

References

  1. Anderson W (1898) A case of angiokeratoma. Br J Dermatol 18:113–117CrossRefGoogle Scholar
  2. 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):384–387PubMedCrossRefGoogle Scholar
  3. Ashwell G, Harford J (1982) Carbohydrate-specific receptors of the liver. Annu Rev Biochem 51:531–554PubMedCrossRefGoogle Scholar
  4. Banikazemi M et al. (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146(2):77–86PubMedGoogle Scholar
  5. Barbey F et al. (2004) Efficacy of enzyme replacement therapy in Fabry disease. Curr Med Chem Cardiovasc Hematol Agents 2(4):277–286PubMedCrossRefGoogle Scholar
  6. Beck M (2002) Agalsidase alfa–a preparation for enzyme replacement therapy in Anderson-Fabry disease. Expert Opin Investig Drugs 11(6):851–858PubMedCrossRefGoogle Scholar
  7. 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 45–50Google Scholar
  8. 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–c38PubMedCrossRefGoogle Scholar
  9. 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):289–297PubMedCrossRefGoogle Scholar
  10. 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):4–12PubMedCrossRefGoogle Scholar
  11. 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):23–31PubMedCrossRefGoogle Scholar
  12. 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):353–358PubMedCrossRefGoogle Scholar
  13. Brady RO et al. (1967) Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med 276(21):1163–1167PubMedCrossRefGoogle Scholar
  14. 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):122–138CrossRefGoogle Scholar
  15. Brooks SA (2004) Appropriate glycosylation of recombinant proteins for human use: implications of choice of expression system. Mol Biotechnol 28(3):241–255PubMedCrossRefGoogle Scholar
  16. 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):479–484PubMedCrossRefGoogle Scholar
  17. Casadevall N et al. (2002) Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 346(7):469–475PubMedCrossRefGoogle Scholar
  18. Chimenti C et al. (2004) Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation 110(9):1047–1053PubMedCrossRefGoogle Scholar
  19. 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):11736–11741PubMedCrossRefGoogle Scholar
  20. Christensen EI (2002) Pathophysiology of protein and vitamin handling in the proximal tubule. Nephrol Dial Transplant 17(Suppl 9):57–58PubMedCrossRefGoogle Scholar
  21. 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):698–706PubMedCrossRefGoogle Scholar
  22. Clark AT et al. (2009) Successful oral tolerance induction in severe peanut allergy. Allergy 64(8):1218–1220PubMedCrossRefGoogle Scholar
  23. Clarke JT et al. (2007) The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease. Genet Med 9(8):504–509PubMedCrossRefGoogle Scholar
  24. 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 2741–2784Google Scholar
  25. 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):9–16PubMedCrossRefGoogle Scholar
  26. 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):711–722PubMedCrossRefGoogle Scholar
  27. Fabry J (1898) Ein Beitrag zur Kenntnis der Purpura haemorrhagica nodularis (Purpura papulosa haemorrhagica Hebrae). Arch Dermatol Syph 43:187–200CrossRefGoogle Scholar
  28. Fineberg SE et al. (1983) Immunogenicity of recombinant DNA human insulin. Diabetologia 25(6):465–469PubMedCrossRefGoogle Scholar
  29. Galili U et al. (1996) Enhancement of antigen presentation of influenza virus hemagglutinin by the natural human anti-Gal antibody. Vaccine 14(4):321–328PubMedCrossRefGoogle Scholar
  30. Garman SC, Garboczi DN (2004) The molecular defect leading to Fabry disease: structure of human a-galactosidase. J Mol Biol 337(2):319–335PubMedCrossRefGoogle Scholar
  31. 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):1547–1557PubMedCrossRefGoogle Scholar
  32. Ghaderi D et al. (2010) Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol 28(8):863–867PubMedCrossRefGoogle Scholar
  33. 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):4–9PubMedCrossRefGoogle Scholar
  34. Gold KF et al. (2002) Quality of life of patients with Fabry disease. Qual Life Res 11(4):317–327PubMedCrossRefGoogle Scholar
  35. Gribben JG et al. (1990) Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 335(8687):434–437PubMedCrossRefGoogle Scholar
  36. 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):261–268CrossRefGoogle Scholar
  37. 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):535–542PubMedCrossRefGoogle Scholar
  38. Howard JG, Mitchison NA (1975) Immunological tolerance. Prog Allergy 18:43–96PubMedGoogle Scholar
  39. Huby RD, Dearman RJ, Kimber I (2000) Why are some proteins allergens? Toxicol Sci 55(2):235–246PubMedCrossRefGoogle Scholar
  40. 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):153–158PubMedCrossRefGoogle Scholar
  41. Hunt SV (2009) Perspectives from B cellimmunology: fact and fancyGoogle Scholar
  42. Ioannou YA et al. (1998) Human a-galactosidase A: glycosylation site 3 is essential for enzyme solubility. Biochem J 332(Pt 3):789–797PubMedGoogle Scholar
  43. Jenkins N, Parekh RB, James DC (1996) Getting the glycosylation right: implications for the biotechnology industry. Nat Biotechnol 14(8):975–981PubMedCrossRefGoogle Scholar
  44. 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):829–834PubMedCrossRefGoogle Scholar
  45. Keating GM, Simpson D (2007) Agalsidase Beta: a review of its use in the management of Fabry disease. Drugs 67(3):435–455PubMedCrossRefGoogle Scholar
  46. Kishnani PS et al. (2010) Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab 99(1):26–33PubMedCrossRefGoogle Scholar
  47. Kleinert J et al. (2009) Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria. Transpl Int 22(3):287–292PubMedCrossRefGoogle Scholar
  48. Lee K et al. (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 13(4):305–313PubMedCrossRefGoogle Scholar
  49. Linhart A, Elliott PM (2007) The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart 93(4):528–535PubMedCrossRefGoogle Scholar
  50. 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):1581–1584PubMedCrossRefGoogle Scholar
  51. Linthorst GE et al. (2004) Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 66(4):1589–1595PubMedCrossRefGoogle Scholar
  52. Linthorst GE et al. (2010) Screening for Fabry disease in high-risk populations: a systematic review. J Med Genet 47(4):217–222PubMedCrossRefGoogle Scholar
  53. 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):256–264PubMedCrossRefGoogle Scholar
  54. Lusher JM (2000) Inhibitor antibodies to factor VIII and factor IX: management. Semin Thromb Hemost 26(2):179–188PubMedCrossRefGoogle Scholar
  55. 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):769–775PubMedCrossRefGoogle Scholar
  56. 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):750–760PubMedCrossRefGoogle Scholar
  57. 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):329–339PubMedCrossRefGoogle Scholar
  58. Meager A (1994) Human antibodies to insulin in diabetes. J Interferon Res 14(4):181–182PubMedCrossRefGoogle Scholar
  59. Mehta A, Hughes DA (2008) Anderson-Fabry disease. alpha-galactosidase A deficiency. Includes: classic Fabry disease, atypical variants of Fabry disease. GeneReviewsGoogle Scholar
  60. 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):236–242PubMedCrossRefGoogle Scholar
  61. Mehta A et al. (2008) Enzyme replacement therapy in Fabry disease: comparison of agalsidase alfa and agalsidase beta. Mol Genet Metab 95(1–2):114–115PubMedCrossRefGoogle Scholar
  62. Meikle PJ et al. (1999) Prevalence of lysosomal storage disorders. JAMA 281(3):249–254PubMedCrossRefGoogle Scholar
  63. 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):595–603PubMedGoogle Scholar
  64. Nalivaeva NN, Turner AJ (2001) Post-translational modifications of proteins: acetylcholinesterase as a model system. Proteomics 1(6):735–747PubMedCrossRefGoogle Scholar
  65. 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):59–62PubMedGoogle Scholar
  66. 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):271–273PubMedCrossRefGoogle Scholar
  67. 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):313–318PubMedCrossRefGoogle Scholar
  68. 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):9505–9510PubMedCrossRefGoogle Scholar
  69. 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):1920–1925PubMedCrossRefGoogle Scholar
  70. Pinto R et al. (2004) Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 12(2):87–92PubMedCrossRefGoogle Scholar
  71. Poorthuis BJ et al. (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105(1–2):151–156PubMedGoogle Scholar
  72. Porter S (2001) Human immune response to recombinant human proteins. J Pharm Sci 90(1):1–11PubMedCrossRefGoogle Scholar
  73. Prabhakar SS, Muhlfelder T (1997) Antibodies to recombinant human erythropoietin causing pure red cell aplasia. Clin Nephrol 47(5):331–335PubMedGoogle Scholar
  74. Quesada JR et al. (1985) Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol 3(11):1522–1528PubMedGoogle Scholar
  75. Richards SM (2002) Immunologic considerations for enzyme replacement therapy in the treatment of lysosomal storage disorders. Clin Applied Immunol Rev 2:241–253CrossRefGoogle Scholar
  76. Richards SM, Olson TA, McPherson JM (1993) Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. Blood 82(5):1402–1409PubMedGoogle Scholar
  77. Ries M et al. (2006) Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 118(3):924–932PubMedCrossRefGoogle Scholar
  78. 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):1222–1230PubMedCrossRefGoogle Scholar
  79. Rolfs A et al. (2005) Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 366(9499):1794–1796PubMedCrossRefGoogle Scholar
  80. 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):2081–2088PubMedGoogle Scholar
  81. Rossman HS (2004) Neutralizing antibodies to multiple sclerosis treatments. J Manag Care Pharm 10(3 Suppl B):S12–S19PubMedGoogle Scholar
  82. 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):180–188PubMedCrossRefGoogle Scholar
  83. Schellekens H (2002) Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 24(11):1720–1740PubMedCrossRefGoogle Scholar
  84. Schellekens H (2003) Immunogenicity of therapeutic proteins. Nephrol Dial Transplant 18(7):1257–1259PubMedCrossRefGoogle Scholar
  85. Schellekens H (2005) Factors influencing the immunogenicity of therapeutic proteins. Nephrol Dial Transplant 20(Suppl 6):vi3–vi9PubMedCrossRefGoogle Scholar
  86. Schellekens H (2008) The immunogenicity of therapeutic proteins and the Fabry antibody standardization initiative. Clin Ther 30:50–51CrossRefGoogle Scholar
  87. Schellekens H, Casadevall N (2004) Immunogenicity of recombinant human proteins: causes and consequences. J Neurol 251(Suppl 2):II4–II9PubMedGoogle Scholar
  88. Schiffmann R et al. (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285(21):2743–2749PubMedCrossRefGoogle Scholar
  89. 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):345–354PubMedCrossRefGoogle Scholar
  90. 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):1576–1583PubMedCrossRefGoogle Scholar
  91. Sharma B (2007) Immunogenicity of therapeutic proteins. Part 3: impact of manufacturing changes. Biotechnol Adv 25(3):325–331PubMedCrossRefGoogle Scholar
  92. Sirrs S, et al. (2009) Baseline characteristics of patients enrolled in the Canadian Fabry Disease Initiative. Mol Genet MetabGoogle Scholar
  93. Sorensen PS et al. (2005) Appearance and disappearance of neutralizing antibodies during interferon-beta therapy. Neurology 65(1):33–39PubMedCrossRefGoogle Scholar
  94. Spada M et al. (2006) High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 79(1):31–40PubMedCrossRefGoogle Scholar
  95. 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):1042–1049PubMedCrossRefGoogle Scholar
  96. 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):1933–1946PubMedCrossRefGoogle Scholar
  97. 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):70–76PubMedGoogle Scholar
  98. Vedder AC et al. (2007a) The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 30(1):68–78PubMedCrossRefGoogle Scholar
  99. 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):e598PubMedCrossRefGoogle Scholar
  100. 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):319–325PubMedCrossRefGoogle Scholar
  101. 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):790–796PubMedCrossRefGoogle Scholar
  102. Wang J et al. (2008) Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat Biotechnol 26(8):901–908PubMedCrossRefGoogle Scholar
  103. Whitfield PD et al. (2005) Monitoring enzyme replacement therapy in Fabry disease - role of urine globotriaosylceramide. J Inherit Metab Dis 28(1):21–33PubMedCrossRefGoogle Scholar
  104. 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):441–449PubMedCrossRefGoogle Scholar
  105. Wight J, Paisley S, Knight C (2003) Immune tolerance induction in patients with haemophilia A with inhibitors: a systematic review. Haemophilia 9(4):436–463PubMedCrossRefGoogle Scholar
  106. Wilcox WR et al. (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75(1):65–74PubMedCrossRefGoogle Scholar
  107. 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 e1Google Scholar
  108. Young E et al. (2005) Is globotriaosylceramide a useful biomarker in Fabry disease? Acta Paediatr Suppl 94(447):51–54, discussion 37–8PubMedCrossRefGoogle Scholar
  109. Zhu A, Hurst R (2002) Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation 9(6):376–381PubMedCrossRefGoogle Scholar
  110. 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):492–500PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  1. 1.Department of MedicineAddenbrooke’s HospitalCambridgeUK

Personalised recommendations