OBJECTIVE: To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3). STUDY DESIGN: Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified. RESULTS: Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis. CONCLUSIONS: Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.
OBJECTIVE: To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant humanalpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3). STUDY DESIGN: Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified. RESULTS: Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis. CONCLUSIONS: Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.
Authors: William R Wilcox; Ulla Feldt-Rasmussen; Ana Maria Martins; Alberto Ortiz; Roberta M Lemay; Ana Jovanovic; Dominique P Germain; Carmen Varas; Katherine Nicholls; Frank Weidemann; Robert J Hopkin Journal: JIMD Rep Date: 2017-05-17
Authors: Frank Weidemann; Johannes Krämer; Thomas Duning; Malte Lenders; Sima Canaan-Kühl; Alice Krebs; Hans Guerrero González; Claudia Sommer; Nurcan Üçeyler; Markus Niemann; Stefan Störk; Michael Schelleckes; Stefanie Reiermann; Jörg Stypmann; Stefan-Martin Brand; Christoph Wanner; Eva Brand Journal: J Am Soc Nephrol Date: 2014-02-20 Impact factor: 10.121
Authors: Uma Ramaswami; Behzad Najafian; Arrigo Schieppati; Michael Mauer; Daniel G Bichet Journal: Clin J Am Soc Nephrol Date: 2010-01-07 Impact factor: 8.237