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Effects of agalsidase-β administration on vascular function and blood pressure in familial Anderson–Fabry disease

European Journal of Human Genetics volume 29, pages 218–224 (2021)Cite this article

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Abstract

Fabry is an X-linked disorder of glycosphingolipid metabolism that is caused by variants of the GLA gene that codes for α-galactosidase A, leading to lysosomal accumulation of globotriaosylceramide in many cell types. As a result, affected patients manifest with an increased risk of developing ischemic stroke, peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. The protective effects of enzyme replacement therapy (ERT), the milestone in Fabry disease treatment, against globotriaosylceramide (GL-3) accumulation and Fabry disease progression are well known. However, the mechanism of action of ERT is not well understood. Since GL-3 also accumulates in the vascular endothelium, we investigated the effects of agalsidase-β, a recombinant human α-Gal enzyme approved for the treatment of Fabry disease. In this study, vascular function and blood pressure in four adult siblings affected by Fabry disease were evaluated upon agalsidase-β. In all patients, agalsidase-β infusion improves flow-mediated dilation and augmentation index. These changes occurred after the first infusion and were then maintained for the whole period of observation, i.e., 1 year, with more pronounced additional increments in flow-mediated dilation after the second agalsidase-β infusion. Blood pressure was also maintained at optimal levels in all of the patients for the whole period of observation. Our findings show that agalsidase-β administration can improve vascular function in patients suffering from Fabry disease. Changes in flow-mediated dilation and augmentation index persisted for the whole period of observation (1 year), thus suggesting that early substitutive therapy should be promoted in order to protect the cardiovascular system.

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Fig. 1: Aix and FMD data for all the four Fabry patients.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    Cosimo Andrea Stamerra, Martina De Feo, Vanessa Castelli, Michele d’Angelo, Annamaria Cimini, Davide Grassi & Claudio Ferri

  2. Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA

    Annamaria Cimini

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  1. Cosimo Andrea Stamerra
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  2. Martina De Feo
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  3. Vanessa Castelli
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Correspondence to Claudio Ferri.

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Stamerra, C.A., De Feo, M., Castelli, V. et al. Effects of agalsidase-β administration on vascular function and blood pressure in familial Anderson–Fabry disease. Eur J Hum Genet 29, 218–224 (2021). https://doi.org/10.1038/s41431-020-00721-9

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