Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] Journal article | | Title | Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. | | Author(s) | Lubanda JC, Anijalg E, Bzdúch V, Thurberg BL, Bénichou B, Tylki-Szymanska A | | Institution | From the 1Clinical Department of Cardiology and Angiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic; 2Department of Internal Medicine, Tartu University Clinics, Tartu, Estonia; 3Department of Pediatrics, Comenius University Children's Hospital, Bratislava, Slovak Republic; 4Genzyme Corporation, Cambridge, Massachusetts; 5Genzyme Europe, Saint-Germain-en-Laye, France; and the 6Clinic of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Warsaw, Poland. | | Source | Genet Med 2009 Mar 4. | | Abstract | 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(R), 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19265719 |
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