PURPOSE: Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated. This study explored whether a lower dose could maintain globotriaosylceramide clearance achieved with 1.0 mg/kg. METHODS: Cellular globotriaosylceramide levels were assessed histologically in kidney and skin biopsies from 21 adult Fabry males treated for 6 months at 1.0 mg/kg/2 weeks followed by 18 months at 0.3 mg/kg/2 weeks. RESULTS: In kidney interstitial capillary endothelium, the primary endpoint, globotriaosylceramide clearance was achieved in 100% of patients with 1.0 mg/kg and maintained in 90% with 0.3 mg/kg. In seven other renal cell types and superficial dermal capillary endothelium, globotriaosylceramide reduction or clearance was maintained with 0.3 mg/kg in approximately 70% of patients. CONCLUSIONS: A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated.

Clinical Department of Cardiology and Angiology Charles University Prague 1st Faculty of Medicine Prague Czech Republic