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.
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.
Authors: Joanna Ghali; Kathy Nicholls; Charles Denaro; David Sillence; Ian Chapman; Jack Goldblatt; Mark Thomas; Janice Fletcher Journal: JIMD Rep Date: 2011-09-15
Authors: Gabor E Linthorst; Alessandro P Burlina; Franco Cecchi; Timothy M Cox; Janice M Fletcher; Ulla Feldt-Rasmussen; Roberto Giugliani; Carla E M Hollak; Gunnar Houge; Derralynn Hughes; Iikka Kantola; Robin Lachmann; Monica Lopez; Alberto Ortiz; Rossella Parini; Alberto Rivera; Arndt Rolfs; Uma Ramaswami; Einar Svarstad; Camilla Tondel; Anna Tylki-Szymanska; Bojan Vujkovac; Steven Waldek; Michael West; F Weidemann; Atul Mehta Journal: JIMD Rep Date: 2012-07-14
Authors: Saskia M Rombach; Bouwien E Smid; Gabor E Linthorst; Marcel G W Dijkgraaf; Carla E M Hollak Journal: J Inherit Metab Dis Date: 2014-02-04 Impact factor: 4.982
Authors: Rannveig Skrunes; Camilla Tøndel; Sabine Leh; Kristin Kampevold Larsen; Gunnar Houge; Einar Skulstad Davidsen; Carla Hollak; André B P van Kuilenburg; Frédéric M Vaz; Einar Svarstad Journal: Clin J Am Soc Nephrol Date: 2017-06-16 Impact factor: 8.237