Current and experimental therapeutics for Fabry disease

Clin Genet. 2021 Sep;100(3):239-247. doi: 10.1111/cge.13999.

PMID: 33997974

Vanessa Castelli, Cosimo Andrea Stamerra, Michele d'Angelo

Highlights: The focus of this review is describing the in vitro and the in vivo experimental models of Fabry disease, to highlight the relevance in improving the existing therapeutics and understand the mechanism of this rare disorder.

Abstract

Background: Males and females can both be affected by the uncommon pan-ethnic disease Fabry (or Anderson-Fabry). X-linked lysosomal storage disease Fabry is brought on by mutations in the GLA gene, which encodes the enzyme -galactosidase A. It affects glycosphingolipid metabolism. Fabry disease (FD) can be divided into two types: a severe, classical (earlier-onset) phenotype that typically manifests before the age of 18 and is most frequently observed in men with no residual enzyme activity; and a milder, nonclassical (later-onset) phenotype that typically manifests after the age of 18. Multifactorial complications in affected patients include renal failure, cardiac problems, and neuropathy.

Objective: This article briefly summarizes the clinical trials that have been conducted so far with using the available therapies in this review, and then we concentrate on the in vitro and in vivo experimental disease models to emphasize their importance for improving the current therapeutics and comprehending the mechanism of this uncommon disorder.

Conclusion: Current in vivo and in vitro models can help with a better understanding of the pathophysiology and underlying mechanisms of FD, allowing for the optimization of current therapy techniques and the development of new possibilities.

Keywords: Fabry disease, enzyme replacement therapy, in vitro models, in vivo models, lysosomal storage disorder, therapeutic approaches