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Re: Myocardial reduction of Gb3 content in Anderson-Fabry disease

Dear Editor,

We read with interest the study by Hughes et al (1) that for the first time showed a reduction of Gb3 content in endomyocardial biopsy tissue of patients with Fabry cardiomyopathy after six months agalsidase alfa treatment.

However, it should be point out that this study doesn’t demonstrate the efficacy of enzyme replacement therapy in clearing the Gb3 deposits from the cardiomyocytes, that is a focal issue in the treatment of Fabry disease cardiomyopathy. In fact, it has been recently shown in an experimental model of Fabry disease that after intravenous injection of agalsidase alfa the enzyme is detectable in myocardial capillaries but not in cardiomyocytes (2). In this setting the reduction in Gb3 content in the heart could be interpreted as the result of clearance from other cell types, particularly endothelial cells. In addition blood contamination could be the source of Gb3 changes, since the plasma Gb3 levels decreased of 45% after treatment (1).

In this context, the reduction in myocardial mass could be related to a progression of the disease with increased fibrosis and reduction in myocardial thickness.

Probably, an immunohistochemical demonstration in endomyocardial biopsy tissue of Gb3 cellular distribution and changes after six months of treatment could have been useful in a better understanding of the study results and it’s desirable in future follow-up studies.

References

1. Hughes DA, Elliott PM, Shah J, Zuckerman J, Coughlan G, Brookes J, Mehta AB.
Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomized, double-blind, placebo-controlled clinical trial of agalsidase-alfa.
Heart 2007 May 4; [Epub ahead of print].