Lucerastat, an iminosugar for substrate reduction therapy in Fabry disease: preclinical evidence

Conference item

Fabry disease (FD) is a lysosomal 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 (SRT) with lucerastat, an orally-available small molecule inhibitor of glucosylceramide synthase (GCS) to reduce Gb3 accumulation is an alternative mechanism, that would be suitable for all FD patients.

Authors: Priestman, D; Welford, R; Platt, F; Muhlemann, A; Garzotti, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Host title: 13th Annual WORLDSymposium
• Journal: WORLDSymposium
• Publication date: 2017-02-01
• Acceptance date: 2017-01-06
• DOI: 10.1016/j.ymgme.2016.11.369