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BioDrugs

, Volume 26, Issue 5, pp 335–354 | Cite as

Agalsidase Alfa

A Review of its Use in the Management of Fabry Disease
  • Gillian M. Keating
Adis Drug Evaluation

Abstract

The enzyme replacement therapy agalsidase alfa (Replagal®) has an amino acid sequence identical to that of native α-galactosidase A; intravenous agalsidase alfa 0.2 mg/kg every other week is indicated for the long-term treatment of patients with confirmed Fabry disease. This article reviews the efficacy and tolerability of agalsidase alfa in patients with Fabry disease, as well as summarizing its pharmacologic properties.

Agalsidase alfa had beneficial effects in adult men with Fabry disease, according to the results of two randomized, double-blind, placebo-controlled, 6-month trials (n= 15 and 26). For example, left ventricular mass index was reduced to a significantly greater extent with agalsidase alfa than with placebo. Although the change in myocardial globotriaosylceramide content (primary endpoint in one study) did not significantly differ between agalsidase alfa and placebo recipients, the change in the Brief Pain Inventory (BPI) ‘pain at its worst’ score (reflecting neuropathic pain while without pain medications; primary endpoint in the second study) was improved to a significantly greater extent with agalsidase alfa than with placebo. In addition, the change in creatinine clearance, but not inulin clearance, significantly favored agalsidase alfa versus placebo recipients. Abnormalities in functional cerebral blood flow and cerebrovascular responses were also reversed with agalsidase alfa therapy.

In extensions of these placebo-controlled trials, the reduction in left ventricular mass and improvements in BPI pain scores were maintained after longer-term agalsidase alfa therapy. The significant decline in estimated glomerular filtration rate (eGFR) seen after 48 months’ agalsidase alfa treatment was mainly driven by a marked decline in eGFR seen in four patients with stage 3 chronic kidney disease at baseline (although the progression of decline appeared slower than that seen in historic controls); renal function appeared stable in patients with stage 1 or 2 chronic kidney disease. Certain benefits of agalsidase alfa became apparent with longer-term therapy. For example, a significant reduction in cold and warm detection thresholds and a significant improvement in sweat function were seen after 3 years’ therapy.

Final results from a head-to-head trial comparing the effects of agalsidase alfa and agalsidase beta at approved dosages are not yet available. The only available fully published study compared agalsidase alfa 0.2 mg/kg every other week with an off-label dosage of agalsidase beta 0.2 mg/kg every other week. This randomized, open-label, 24-month trial in adult men and women with Fabry disease generally found no significant differences in outcome between treatment arms. It should be noted that concerns were subsequently raised by the European Medicines Agency regarding the use of agalsidase beta at dosages other than the approved dosage of 1 mg/kg every other week. Preliminary results from an ongoing, randomized, open-label study suggest no differences in outcome between patients with Fabry disease receiving intravenous agalsidase alfa 0.2 mg/kg every other week and those receiving the approved regimen of agalsidase beta 1 mg/kg every other week. In three switching studies, no safety concerns were raised and disease stability was generally maintained following the switch from agalsidase beta 1 mg/kg every other week to agalsidase alfa 0.2 mg/kg every other week.

Agalsidase alfa also demonstrated beneficial effects, including in women and pediatric patients, in non-comparative studies and in the Fabry Outcome Survey.

Agalsidase alfa was generally well tolerated in patients with Fabry disease, with infusion reactions (e.g. rigors, pyrexia, flushing) being the most commonly occurring adverse event. IgG antibodies developed in ≈24% of male patients with Fabry disease who received agalsidase alfa. After 12–54 months of treatment, 17% of agalsidase alfa recipients were still IgG antibody positive, with immunologic tolerance developing in 7% of agalsidase alfa recipients. No IgE antibodies have been detected in any patient receiving agalsidase alfa. No antibody formation was reported in women receiving agalsidase alfa in noncomparative studies.

In conclusion, agalsidase alfa is an effective and well tolerated treatment option for use in patients with Fabry disease.

Keywords

Neuropathic Pain Enzyme Replacement Therapy Fabry Disease Infusion Reaction Noncomparative Study 
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.

References

  1. 1.
    Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. QJM Mon J Assoc Physicians 2010 Sep; 103(9): 641–59CrossRefGoogle Scholar
  2. 2.
    Hughes DA, Ramaswam U, Elliott P, et al. Guidelines for the diagnosis and management of Anderson-Fabry disease [online]. Available from URL: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_4118408.pdf [Accessed 2012 May 3]
  3. 3.
    Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006 Jul; 79(1): 31–40PubMedCrossRefGoogle Scholar
  4. 4.
    Ortiz A, Oliveira JP, Wanner C, et al. Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults. Nat Clin Pract Nephrol 2008 Jun; 4(6): 327–36PubMedCrossRefGoogle Scholar
  5. 5.
    Ries M, Clarke JT, Whybra C, et al. Enzyme replacement in Fabry disease: pharmacokinetics and pharmacodynamics of agalsidase alfa in children and adolescents. J Clin Pharmacol 2007 Oct; 47(10): 1222–30PubMedCrossRefGoogle Scholar
  6. 6.
    Lee K, Jin X, Zhang K, et al. A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 2003 Apr; 13(4): 305–13PubMedCrossRefGoogle Scholar
  7. 7.
    European Medicines Agency. European public assessment report for Replagal: scientific discussion [online]. Available from URL: http://www.ema.europa.eu [Accessed 2012 Apr 24]
  8. 8.
    European Medicines Agency. Replagal (agalsidase alfa): EU summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000369/WC500053612.pdf [Accessed 2012 Apr 24]
  9. 9.
    Sakuraba H, Murata-Ohsawa M, Kawashima I, et al. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibro-blasts and Fabry mice. J Hum Genet 2006 Mar; 51(3): 180–8PubMedCrossRefGoogle Scholar
  10. 10.
    Schiffmann R, Murray GJ, Treco D, et al. Infusion of a-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A 2000 Jan 4; 97(1): 365–70PubMedCrossRefGoogle Scholar
  11. 11.
    Clarke JTR, West ML, Bultas J, et al. The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease. Genet Med 2007 Aug; 9(8): 504–9PubMedCrossRefGoogle Scholar
  12. 12.
    Gal A, Hughes DA, Winchester B. Toward a consensus in the laboratory diagnostics of Fabry disease: recommendations of a European expert group. J Inherit Metab Dis 2011 Apr; 34(2): 509–14PubMedCrossRefGoogle Scholar
  13. 13.
    Pastores GM, Boyd E, Crandall K, et al. Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 2007 July; 22(7): 1920–5PubMedCrossRefGoogle Scholar
  14. 14.
    Murray GJ, Anver MR, Kennedy MA, et al. Cellular and tissue distribution of intravenously administered agalsidase alfa. Mol Genet Metab 2007 Mar; 90(3): 307–12PubMedCrossRefGoogle Scholar
  15. 15.
    Schiffmann R, Kopp JB, Austin III IHA, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001 Jun 6; 285(21): 2743–9PubMedCrossRefGoogle Scholar
  16. 16.
    Hughes DA, Elliott PM, Shah J, et al. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 2008 Feb; 94(2): 153–8PubMedCrossRefGoogle Scholar
  17. 17.
    Schiffmann R, Hauer P, Freeman B, et al. Enzyme replacement therapy and intraepidermal innervation density in Fabry disease. Muscle Nerve 2006 Jul; 34(1): 53–6PubMedCrossRefGoogle Scholar
  18. 18.
    Schiffmann R, Floeter MK, Dambrosia JM, et al. Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 2003 Dec; 28(6): 703–10PubMedCrossRefGoogle Scholar
  19. 19.
    Moore DF, Scott LTC, Gladwin MT, et al. Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 2001 Sep 25; 104(13): 1506–12PubMedCrossRefGoogle Scholar
  20. 20.
    Moore DF, Altarescu G, Ling GSF, et al. Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 2002 Feb; 33(2): 525–31PubMedCrossRefGoogle Scholar
  21. 21.
    Moore DF, Altarescu G, Herscovitch P, et al. Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease. BMC Neurol 2002 Jun 18; 2: 4PubMedCrossRefGoogle Scholar
  22. 22.
    Schiffmann R, Ries M, Timmons M, et al. Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 2006 Feb; 21(2): 345–54PubMedCrossRefGoogle Scholar
  23. 23.
    Hajioff D, Goodwin S, Quiney R, et al. Hearing improvement in patients with Fabry disease treated with agalsidase alfa. Acta Paediatr Suppl 2003 Dec; 92(443): 28–30PubMedGoogle Scholar
  24. 24.
    Schiffmann R, Askari H, Timmons M, et al. 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 2007 May; 18(5): 1576–83PubMedCrossRefGoogle Scholar
  25. 25.
    West M, Nicholls K, Mehta A, et al. Agalsidase alfa and kidney dysfunction in Fabry disease. J Am Soc Nephrol 2009 May; 20(5): 1132–9PubMedCrossRefGoogle Scholar
  26. 26.
    Vedder AC, Linthorst GE, Houge G, et al. Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PloS One 2007 Jul; 2(7): e598PubMedCrossRefGoogle Scholar
  27. 27.
    Genzyme Corporation. Fabrazyme (agalsidase beta): US prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103979s51351bl.pdf [Accessed 2012 May 3]
  28. 28.
    European Medicines Agency. Fabrazyme (agalsidase beta): EU summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000370/WC500020547.pdf [Accessed 2012 May 3]
  29. 29.
    European Medicines Agency. Assessment report for Fabrazyme (agalsidase beta) [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/11/WC500099241.pdf [Accessed 2012 Jul 10]
  30. 30.
    West M, Bichet DG, Casey R, et al. Prospective results of switching enzyme replacement therapy from agalsidase beta to agalsidase alfa in the Canadian Fabry Disease Initiative study [abstract no. 197]. 8th Annual Lysosomal Disease Network World Symposium; 2012 Feb 8–10; San Diego (CA)Google Scholar
  31. 31.
    Sirrs S, Clarke JTR, Bichet DG, et al. Baseline characteristics of patients enrolled in the Canadian Fabry Disease Initiative. Mol Genet Metab 2010 Apr; 99(4): 367–73PubMedCrossRefGoogle Scholar
  32. 32.
    Canadian Fabry Research Consortium. Canadian Fabry Disease Initiative (CFDI) enzyme replacement therapy (ERT) study [ClinicalTrials.gov identifier NCT00455104]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 May 4]
  33. 33.
    West M, LeMoine K, Bichet D, et al. A randomized controlled trial of enzyme replacement therapy in Fabry nephropathy: the Canadian Fabry Disease Initiative at year two [abstract]. Clin Ther 2010; 32 Suppl. C: S115–S6Google Scholar
  34. 34.
    West M, Bichet D, Casey R, et al. Agalsidase alfa and agalsidase beta have similar effects on outcomes in Fabry disease: results from the Canadian Fabry Disease Initiative [abstract]. Mol Genet Metab 2011; 102: S46CrossRefGoogle Scholar
  35. 35.
    Alpan-Goker O, Nedd K, Shankar S, et al. Effect and tolerability of agalsidase alfa in patients with Fabry disease who were treatment-naïve or formerly treated with agalsidase beta [abstract]. Annual Clinical Genetics Meeting; 2012 Mar 27–31; Charlotte (NC)Google Scholar
  36. 36.
    Goker-Alpan O, Nedd K, Shankar S, et al. Effect and tolerability of agalisdase alfa in patients with Fabry disease [abstract]. Society for the Study of Inborn Errors of Metabolism Annual Symposium; 2012 Sep 4–7; BirminghamGoogle Scholar
  37. 37.
    Tsuboi K, Yamamoto H. Clinical observation of patients with Fabry disease after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal). Genet Med. Epub 2012 Apr 12Google Scholar
  38. 38.
    Shire Human Genetic Therapies, Inc. Treatment protocol of Replagal for patients with Fabry disease [ClinicalTrials.gov identifier NCT01031173]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Aug 7]
  39. 39.
    Baehner F, Kampmann C, Whybra C, et al. Enzyme replacement therapy in heterozygous females with Fabry disease: results of a phase IIIB study. J Inherit Metab Dis 2003; 26(7): 617–27PubMedCrossRefGoogle Scholar
  40. 40.
    Kampmann C, Linhart A, Devereux RB, et al. Effect of agalsidase alfa replacement therapy on Fabry disease-related hypertrophic cardiomyopathy: a 12- to 36-month, retrospective, blinded echocardiographic pooled analysis. Clin Ther 2009 Sep; 31(9): 1966–76PubMedCrossRefGoogle Scholar
  41. 41.
    Whybra C, Miebach E, Mengel E, et al. A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med 2009 Jun; 11(6): 441–9PubMedCrossRefGoogle Scholar
  42. 42.
    Parini R, Rigoldi M, Santus F, et al. Enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients with Anderson-Fabry disease: testing the effects with the Mainz Severity Score Index. Clin Genet 2008; 74(3): 260–6PubMedCrossRefGoogle Scholar
  43. 43.
    Thofehrn S, Netto C, Cecchin C, et al. Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience. Ren Fail 2009 Oct; 31(9): 773–8PubMedCrossRefGoogle Scholar
  44. 44.
    Dehout F, Roland D, Treille de Granseigne S, et al. Relief of gastrointestinal symptoms under enzyme replacement therapy in patients with Fabry disease. J Inherit Metab Dis 2004; 27(4): 499–505PubMedCrossRefGoogle Scholar
  45. 45.
    Ries M, Clarke JTR, Whybra C, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006 Sep; 118(3): 924–32PubMedCrossRefGoogle Scholar
  46. 46.
    Schiffmann R, Martin RA, Reimschisel T, et al. Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease. J Pediatr 2010 May; 156(5): 832–7PubMedCrossRefGoogle Scholar
  47. 47.
    Ramaswami U, Wendt S, Pintos-Morell G, et al. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 2007 Jan; 96(1): 122–7PubMedCrossRefGoogle Scholar
  48. 48.
    Mehta A, Beck M, Elliott P, et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet 2009 Dec 12; 374(9706): 1986–96PubMedCrossRefGoogle Scholar
  49. 49.
    Hoffmann B, Beck M, Sunder-Plassmann G, et al. 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 2007 Jul/Aug; 23(6): 535–42PubMedCrossRefGoogle Scholar
  50. 50.
    Schwarting A, Dehout F, Feriozzi S, et al. Enzyme replacement therapy and renal function in 201 patients with Fabry disease. Clin Nephrol 2006 Aug; 66(2): 77–84PubMedGoogle Scholar
  51. 51.
    Feriozzi S, Schwarting A, Sunder-Plassmann G, et al. Agalsidase alfa slows the decline in renal function in patients with Fabry disease. Am J Nephrol 2009 April; 29(5): 353–61PubMedCrossRefGoogle Scholar
  52. 52.
    Feriozzi S, Torras J, Cybulla M, et al. The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy. C J Am Soc Nephrol 2012 Jan; 7(1): 60–9CrossRefGoogle Scholar
  53. 53.
    Cybulla M, Walter KN, Schwarting A, et al. Kidney transplantation in patients with Fabry disease. Transpl Int 2009 Apr; 22(4): 475–81PubMedCrossRefGoogle Scholar
  54. 54.
    Hajioff D, Hegemann S, Conti G, et al. Agalsidase alpha and hearing in Fabry disease: data from the Fabry Outcome Survey. Eur J Clin Invest 2006; 36: 663–7PubMedCrossRefGoogle Scholar
  55. 55.
    Hoffmann B, Schwarz M, Mehta A, et al. Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol 2007 Dec; 5(12): 1447–53PubMedCrossRefGoogle Scholar
  56. 56.
    Hughes DA, Barba Romero M-A, Hollak CEM, et al. Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS (the Fabry Outcome Survey). Mol Genet Metab 2011 Jul; 103(3): 207–14PubMedCrossRefGoogle Scholar
  57. 57.
    Ramaswami U, Parini R, Pintos-Morell G, et al. Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey. Clin Genet 2012 May; 81(5): 485–90PubMedCrossRefGoogle Scholar
  58. 58.
    Hajioff D, Enever Y, Quiney R, et al. Hearing loss in Fabry disease: the effect of agalsidase alfa replacement therapy. J Inherit Metab Dis 2003; 26(8): 787–94PubMedCrossRefGoogle Scholar
  59. 59.
    Shire Human Genetic Therapies, Inc. Replagal® (agalsidase alfa): Canadian product monograph [online]. Available from URL: http://www.shirecanada.com/en/shire-canada/Replagal_M_080521_En.pdf [Accessed 2012 May 1]
  60. 60.
    Schaefer RM, Tylki-Szymańska A, Hilz MJ. Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 2009; 69(16): 2179–205PubMedCrossRefGoogle Scholar
  61. 61.
    Ramaswami U. Update on role of agalsidase alfa in management of Fabry disease. Drug Des Devel Ther 2011; 5: 155–73PubMedCrossRefGoogle Scholar
  62. 62.
    Beck M. Agalsidase alfa for the treatment of Fabry disease: new data on clinical efficacy and safety. Expert Opin Biol Therapy 2009 Feb; 9(2): 255–61CrossRefGoogle Scholar
  63. 63.
    Desnick RJ, Brady R, Barranger J, et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003 Feb 18; 138(4): 338–46PubMedCrossRefGoogle Scholar
  64. 64.
    Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006 Sep; 8(9): 539–48PubMedCrossRefGoogle Scholar
  65. 65.
    Tøndel C, Bostad L, Hirth A, et al. Renal biopsy findings in children and adolescents with Fabry disease and minimal albuminuria. Am J Kidney Dis 2008 May; 51(5): 767–76PubMedCrossRefGoogle Scholar
  66. 66.
    Keating GM, Simpson D. Agalsidase beta: a review of its use in the management of Fabry disease. Drugs 2007; 67(3): 435–55PubMedCrossRefGoogle Scholar
  67. 67.
    Lubanda J-C, Anijalg E, Bzdúch V, et al. Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 2009 Apr; 11(4): 256–64PubMedCrossRefGoogle Scholar
  68. 68.
    Genzyme Corporation. Genzyme announces FDA approval of Framingham manufacturing plant [media release]. Available from URL: http://www.businesswire.com/news/genzyme/20120123006531/en [Accessed 2012 May 4]
  69. 69.
    Linthorst GE, Germain DP, Hollak CEM, et al. Expert opinion on temporary treatment recommendations for Fabry disease during the shortage of enzyme replacement therapy (ERT). Mol Genet Metab 2011 Jan; 102(1): 99–102PubMedCrossRefGoogle Scholar
  70. 70.
    Deegan PB. Fabry disease, enzyme replacement therapy and the significance of antibody responses. J Inherit Metab Dis 2012 Mar; 35(2): 227–43PubMedCrossRefGoogle Scholar
  71. 71.
    Vedder AC, Breunig F, Donker-Koopman WE, et al. Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3. Mol Genet Metab 2008 Jul; 94(3): 319–25PubMedCrossRefGoogle Scholar
  72. 72.
    Linthorst GE, Hollak CEM, Donker-Koopman WE, et al. Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 2004 Oct; 66(4): 1589–95PubMedCrossRefGoogle Scholar
  73. 73.
    Brinks V, Richards S, Ruiz J, et al. Fabry disease antibody standardization initiative (FASI) [abstract]. Mol Genet Metab 2012; 105: S22–S3CrossRefGoogle Scholar
  74. 74.
    Wendt S, Whybra C, Kampmann C, et al. Successful pregnancy outcome in a patient with Fabry disease receiving enzyme replacement therapy with agalsidase alfa. J Inherit Metab Dis 2005; 28(5): 787–8PubMedCrossRefGoogle Scholar
  75. 75.
    Dehout F, Roland D, Henry F. Successful pregnancy in a patient with Fabry disease receiving enzyme replacement therapy [abstract]. Acta Paediatr 2006; 95 Suppl. 451: 137–8Google Scholar
  76. 76.
    Kalkum G, Macchiella D, Reinke J, et al. Enzyme replacement therapy with agalsidase alfa in pregnant women with Fabry disease. Eur J Obstet Gynecol Reprod Biol 2009 May; 144(1): 92–3PubMedCrossRefGoogle Scholar
  77. 77.
    Marshall J, Ashe KM, Bangari D, et al. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease. PloS One 2010; 5(11): e15033PubMedCrossRefGoogle Scholar
  78. 78.
    Abe A, Gregory S, Lee L, et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest 2000 Jun; 105(11): 1563–71PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

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