Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa

Background: Anderson-Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb(3)) 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 Gb(3) 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 Gb(3) 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.