Fibrosis: a key feature of Fabry disease with potential therapeutic implications

• Type: Another Publication in an International Scientific Journal
• Date: 2013

Authors

Weidemann, F (Author) Other; Sanchez Nino, MD (Author) Other; Politei, J (Author) Other; João Paulo Oliveira (Author) FMUP; Wanner, C (Author) Other; Warnock, DG (Author) Other; Ortiz, A (Author) Other

Journal

Title: Orphanet Journal of Rare Diseases

Vol. 8

Final page: 116

ISSN: 1750-1172

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 114 Citations

Scopus - 123 Citations

Other information

Authenticus ID: P-006-89H

DOI: 10.1186/1750-1172-8-116

Abstract (EN): Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12