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

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 neurop...

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Dades bibliogràfiques
Autors principals: Welford, R, Mühleman, A, Priestman, D, Garzotti, M, Deymier, C, Ertel, E, Iglarz, M, Morand, O, Platt, F, Probst, M
Format: Conference item
Publicat: Karger 2017
Descripció
Sumari: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.