TY - JOUR
T1 - Enzyme therapy in Fabry disease
T2 - Differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic α-galactosidase A isozymes
AU - Desnick, R. J.
AU - Dean, K. J.
AU - Grabowski, G.
AU - Bishop, D. F.
AU - Sweeley, C. C.
PY - 1979
Y1 - 1979
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0008548181&partnerID=8YFLogxK
U2 - 10.1073/pnas.76.10.5326
DO - 10.1073/pnas.76.10.5326
M3 - Article
C2 - 228284
AN - SCOPUS:0008548181
SN - 0027-8424
VL - 76
SP - 5326
EP - 5330
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -