Lucerastat, an iminosugar for substrate reduction therapy in Fabry Disease: Preclinical evidence

Conference item

Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the GLA gene coding for α-galactosidase A (α-GalA). These mutations lead to the accumulation of α-GalA substrates, including globotriaosylceramide (Gb3). As a consequence of lipid storage, Fabry patients can suffer from neuropathic pain, impaired kidney function and cardiomyopathy. Existing treatments for FD either require bi-weekly intravenous infusions of replacement enzyme, or are effective in a limited number of patients with specific “amenable” mutations. Substrate reduction therapy with lucerastat, an orally-available small molecule inhibitor of glucosylceramide synthase (GCS)1 is an alternative mechanism to reduce Gb3 accumulation, that would be suitable for all FD patients.

Authors: Welford, R; Mühleman, A; Priestman, D; Garzotti, M; Deymier, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Karger
• Host title: 5th Update on Fabry Nephropathy
• Journal: 5th Update on Fabry Nephropathy
• Publication date: 2017-04-21
• Acceptance date: 2017-03-15
• DOI: 10.1159/000475511