Eliglustat tartrate is a highly specific inhibitor of glucosylceramide synthase, developed for the treatment glucosylceramide-based glycosphingolipidoses. Eliglustat is in late clinical development for Gaucher disease type 1. Phase II and III clinical trials have demonstrated clinical efficacy for eliglustat as a stand-alone agent for newly diagnosed patients that are naïve to prior therapy and for patients who have been previously treated with enzyme replacement therapy. Importantly, the reported toxicity of eliglustat has been limited. Eliglustat will be submitted for the US FDA and EMA review in late 2013. Several structurally unrelated glucosylceramide synthase inhibitors have been identified and are in various stages of development, some of which cross the blood-brain barrier. Targeting glucosylceramide synthesis is also a promising approach for the treatment of type 2 diabetes mellitus, autosomal dominant polycystic kidney disease and certain cancers.
Keywords: Fabry disease; Gaucher disease; glucosylceramide; glycosphingolipid; polycystic kidney disease; type 2 diabetes mellitus.