Developments in the treatment of Fabry disease

J Inherit Metab Dis. 2020 Sep;43(5):908-921. doi: 10.1002/jimd.12228. Epub 2020 Mar 2.

PMID: 32083331

Sanne J van der Veen, Carla E M Hollak, André B P van Kuilenburg, Mirjam Langeveld

Summary: This review summarizes what is known about present and prospective future therapy options for Fabry disease.

Abstract

Background: For the treatment of Fabry disease, enzyme replacement therapy (ERT) with recombinant α-galactosidase A (r-αGAL A) has been available for over 15 years. Long-term treatment may decrease disease progression, but most patients still develop cardiac, renal, and cerebral problems. Furthermore, intravenous treatment must be continued for the rest of the patient’s life. As a result, throughout the last decade, various innovative therapy techniques have been investigated. The only other presently approved treatment for Fabry disease is chaperone therapy (Migalastat; 1-deoxygalactonojirimycin). This oral small molecule is intended to increase the enzyme activity of mutant α-galactosidase A and is can only be used in patients with specific mutations.

Objective: Second-generation enzyme replacement therapies (Pegunigalsidasealfa, Moss-aGal), substrate reduction therapies (Venglustat and Lucerastat), and mRNA- and gene-based therapy are all currently being studied in (pre)clinical trials. This review summarizes what is known about present and prospective future therapy options for Fabry disease.

Keywords: Fabry disease; chaperone therapy; enzyme replacement therapy (ERT); gene therapy; substrate reduction therapy (SRT); treatment.