Developments in the treatment of Fabry disease

  • J Inherit Metab Dis. 2020 Sep;43(5):908-921. doi: 10.1002/jimd.12228.
Sanne J van der Veen  1 ,  Carla E M Hollak  1 ,  André B P van Kuilenburg  2 ,  Mirjam Langeveld  1
Affiliations
  • 1. Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, AZ, Amsterdam, The Netherlands.
  • 2. Department of Clinical Chemistry, Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, AZ, Amsterdam, The Netherlands.
PMID: 32083331 DOI: 10.1002/jimd.12228
Abstract

Enzyme replacement therapy (ERT) with recombinant α-galactosidase A (r-αGAL A) for the treatment of Fabry disease has been available for over 15 years. Long-term treatment may slow down disease progression, but cardiac, renal, and cerebral complications still develop in most patients. In addition, lifelong intravenous treatment is burdensome. Therefore, several new treatment approaches have been explored over the past decade. Chaperone therapy (Migalastat; 1-deoxygalactonojirimycin) is the only Other currently approved therapy for Fabry disease. This oral small molecule aims to improve enzyme activity of mutated α-galactosidase A and can only be used in patients with specific mutations. Treatments currently under evaluation in (pre)clinical trials are second generation enzyme replacement therapies (Pegunigalsidase-alfa, Moss-aGal), substrate reduction therapies (Venglustat and Lucerastat), mRNA- and gene-based therapy. This review summarises the knowledge on currently available and potential future options for the treatment of Fabry disease.

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