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Clinical trials
Effects of enzyme replacement therapy on the cardiomyopathy of Anderson–Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa
  1. D A Hughes1,
  2. P M Elliott2,
  3. J Shah2,
  4. J Zuckerman3,
  5. G Coghlan4,
  6. J Brookes5,
  7. A B Mehta1
  1. 1
    Department of Haematology, Royal Free Hospital and University College Medical School, London, UK
  2. 2
    The Heart Hospital, London, UK
  3. 3
    Clinical Trials Centre, Royal Free Hospital and University College Medical School, London, UK
  4. 4
    Department of Cardiology, Royal Free Hospital and University College Medical School, London, UK
  5. 5
    Cardiovascular Magnetic Resonance Unit, The Middlesex Hospital, London, UK
  1. Dr D A Hughes, Department of Academic Haematology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK;{at}


Background: Anderson–Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of cells throughout the body that ultimately results in premature death from renal, cardiac or cerebrovascular complications. Until recently, there was no effective therapy available for this disease. The present study was designed to assess the safety and efficacy of enzyme replacement therapy with agalsidase alfa on the cardiac manifestations of Anderson–Fabry disease.

Method: The effects of therapy with agalsidase alfa on cardiac structure and function were assessed in a randomised, double-blind, placebo-controlled study of 15 adult male patients with Anderson–Fabry disease. The following parameters were measured at baseline and 6 months: left ventricular mass, QRS duration and levels of Gb3 in cardiac tissue, urine sediment and plasma. After 6 months of the randomised trial patients were enrolled in a 2-year open-label extension study.

Results: Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p = 0.041). A mean 20% reduction in myocardial Gb3 content as assessed by serial transvenous endomyocardial biopsies was demonstrated over the 6 months of enzyme replacement compared to a mean 10% increase in patients receiving placebo (p = 0.42)

Conclusion: Enzyme replacement therapy with agalsidase alfa resulted in regression of the hypertrophic cardiomyopathy associated with Anderson–Fabry disease.

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  • Competing interests: A Mehta, D Hughes and P Elliott have received travel grants, educational grants, and/or honoraria for speaking engagements from Shire Human Genetics.

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