We compared two recombinant alpha-galactosidases developed for enzyme replacement therapy for Fabry disease, agalsidase alfa and agalsidase beta, as to specific alpha-galactosidase activity, stability in plasma, mannose 6-phosphate (M6P) residue content, and effects on cultured human Fabry fibroblasts and Fabry mice. The specific enzyme activities of agalsidase alfa and agalsidase beta were 1.70 and 3.24 mmol h(-1) mg protein(-1), respectively, and there was no difference in stability in plasma between them. The M6P content of agalsidase beta (3.6 mol/mol protein) was higher than that of agalsidase alfa (1.3 mol/mol protein). The administration of both enzymes resulted in marked increases in alpha-galactosidase activity in cultured human Fabry fibroblasts, and Fabry mouse kidneys, heart, spleen and liver. However, the increase in enzyme activity in cultured fibroblasts, kidneys, heart and spleen was higher when agalsidase beta was used. An immunocytochemical analysis revealed that the incorporated recombinant enzyme degraded the globotriaosyl ceramide accumulated in cultured Fabry fibroblasts in a dose-dependent manner, with the effect being maintained for at least 7 days. Repeated administration of agalsidase beta apparently decreased the number of accumulated lamellar inclusion bodies in renal tubular cells of Fabry mice.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10038-005-0342-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Drug conversion of enzyme replacement for Fabry disease: a case report].
Zhonghua Nei Ke Za Zhi
February 2025
Department of Nephrology, Heze Municipal Hospital, Heze274000,China.
A real-world pharmacovigilance analysis for agalsidase beta: findings from the FDA adverse event reporting database.
Expert Opin Drug Saf
December 2024
Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Fabry disease (FD), an X-linked lysosomal disorder, is marked by a lack of alpha-galactosidase A (α-Gal A). Agalsidase beta, a recombinant form of α-Gal A, is fundamental to enzyme replacement therapy for FD but requires close monitoring for adverse events (AEs).
Research Design And Methods: This study retrospectively analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database for agalsidase beta-related AEs.
Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice.
Adv Ther
December 2024
Cardiovascular Department, ASL8 Arezzo San Donato Hospital, Via Pietro Nenni 20, 52100, Arezzo, Italy.
Article Synopsis
- - Fabry disease (FD) is a rare genetic disorder causing issues in the kidneys, nervous system, and heart, with four treatment options: three enzyme replacement therapies (ERTs) and one pharmacological chaperone.
- - Agalsidase beta and agalsidase alfa improve various organ functions and quality of life, with agalsidase beta possibly being more effective long-term; early treatment is crucial for optimal response.
- - Migalastat benefits patients with specific gene variants by stabilizing kidney function and relieving some symptoms, but its neurological effects are unclear and further research is needed for direct treatment comparisons.
Safety and Tolerability of a Shorter Agalsidase Beta Infusion Time in Patients with Classic or Later-Onset Fabry Disease.
Biomedicines
November 2024
Referral Center for Fabry Disease and Lysosomal Diseases, MetabERN, F-92380 Garches, France.
Article Synopsis
- Fabry disease presents complex challenges in patient care, and while enzyme replacement therapy (agalsidase beta) is beneficial, its long infusion time can be burdensome for patients.
- A study involved 39 adult patients with Fabry disease to evaluate the safety of reducing the infusion time to 90 minutes without premedication, with a total of 85 infusions conducted.
- The findings showed no reported adverse events, stable vital signs, and high patient satisfaction, indicating that shorter infusion times are safe and feasible for patients with Fabry disease.*
Comparative pharmacokinetics and pharmacodynamics of two formulations of agalsidase beta (agalsidase Biosidus) and Fabrazyme® by intravenous infusion in healthy male volunteers.
Mol Genet Metab Rep
December 2024
Biosidus S.A.U, Buenos Aires 1254, Argentina.
Fabry disease is a rare X-linked lysosomal condition that leads to the accumulation of glycosphingolipids in various tissues, causing cellular dysfunction, tissue remodeling, progressive fibrosis, and organ failure. The disease results from a deficiency in the human α-galactosidase A enzyme, responsible for breaking down glycosphingolipids like globotriaosylceramide (GL-3 or Gb3) into galactose and dihexose ceramides. In individuals diagnosed with Fabry disease, treatment from 2 years of age onwards typically involves agalsidase beta, the normal recombinant form of the defective enzyme.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!