Enzyme replacement therapy in Gaucher's disease: a rapid, high-yield method for purification of glucocerebrosidase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 73 ·No. 12 ·1976-12-00 ·Pages 4672-4

Dale GL, Beutler E

Abstract

Gaucher's disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45); this disorder has been a leading candidate for enzyme replacement trials. A rapid, high-yield method for purification of glucocerebrosidase has been developed. Detergent extraction of human placenta was followed by salt fractionation, concanavalin A-Sepharose chromatography, organic solvent precipitation, and affinity chromatography on phosphatidylserine-agarose; the total yield is 60% with 6000-fold purification. Purified glucocerebrosidase has been administered intravenously to a volunteer Gaucher's patient on two separate occasions. For the first injection, the enzyme was entrapped in resealed erythrocytes; for the second injection, the enzyme was given without any carrier. The enzyme infusions caused no untoward effects.

MeSH Terms

Erythrocyte Membrane Gaucher Disease/drug therapy Glucosidases/isolation & purification Glucosylceramidase/administration & dosage,isolation & purification,therapeutic use Humans Injections, Intravenous Methods Placenta/enzymology

Chemicals

Glucosidases Glucosylceramidase

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Dale G L

Beutler E

References (11)

11 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.73.12.4672

Published

1976-12-00

Pages

4672-4

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC431591

Subset

External Links

PubMed source DOI: 10.1073/pnas.73.12.4672 PMC Full Text View journal details

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Enzyme replacement therapy in Gaucher's disease: a rapid, high-yield method for purification of glucocerebrosidase.

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