Enzyme therapy in Fabry disease: Differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic α-galactosidase A isozymes

R. J. Desnick, K. J. Dean, G. Grabowski, D. F. Bishop, C. C. Sweeley

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

A pilot trial of enzyme replacement with splenic and plasma α-galactosidase A (α-D-galactosidase; α-D-galactoside galactohydrolase, EC 3.2.1.22) isozymes was undertaken in two brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Six unentrapped doses (2000 units/kg) of each isozyme were administered intravenously to the respective recipient during a 117-day period. The circulating half-life of the splenic isozyme was about 10 min, whereas that for the plasma isozyme was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either isozyme after successive administrations. After each dose of the splenic isozyme, the concentration of the accumulated circulating substrate, trihexosylceramide (globotriaosylceramide) decreased maximally (~50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma isozyme decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations gradually returned to preinfusion values by 36-72 hr.

Original languageEnglish
Pages (from-to)5326-5330
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume76
Issue number10
DOIs
StatePublished - 1979

Fingerprint

Dive into the research topics of 'Enzyme therapy in Fabry disease: Differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic α-galactosidase A isozymes'. Together they form a unique fingerprint.

Cite this