Correction of the enzymic defect in cultured fibroblasts from patients with Fabry's disease: Treatment with purified α galactosidase from ficin

G. Dawson, Reuben Matalon, Teh Li Yu Teh Li

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cultured skin fibroblasts from patients with Fabry's disease showed the characteristic α galactosidase deficiency and accumulated a four- to sixfold excess of trihexosylceramide (GL-3). To demonstrate the correction, cells previously labeled with U 14C glucose were grown in medium containing a purified α galactosidase preparation obtained from ficin. The results demonstrated that α galactosidase was taken up rapidly from the medium and that, despite its apparent instability in the fibroblasts, it was able to become incorporated into lysosomes and catabolize the stored trihexosylceramide. These findings support the reports of therapeutic endeavors by renal transplantation and plasma infusion in Fabry's disease and suggest the extension of such studies to other related disorders in which the cultured skin fibroblasts are chemically abnormal, namely, Gaucher's disease, lactosylceramidosis, and G(M2) gangliosidosis type II. It may be possible to replace the specific missing lysosomal hydrolase in various spingolipidoses and other storage diseases. Although the authors do not propose to effect enzyme replacement therapy in vivo with a plant enzyme, such studies in tissue culture are valid, and eventually human α galactosidase, of comparable activity and purity, will become available.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalPediatric Research
Volume7
Issue number8
StatePublished - 1973
Externally publishedYes

Fingerprint

Ficain
Galactosidases
Fabry Disease
Trihexosylceramides
Fibroblasts
Sandhoff Disease
Enzyme Replacement Therapy
Gaucher Disease
Skin
Hydrolases
Therapeutics
Lysosomes
Kidney Transplantation
Glucose
Enzymes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Correction of the enzymic defect in cultured fibroblasts from patients with Fabry's disease : Treatment with purified α galactosidase from ficin. / Dawson, G.; Matalon, Reuben; Yu Teh Li, Teh Li.

In: Pediatric Research, Vol. 7, No. 8, 1973, p. 684-690.

Research output: Contribution to journalArticle

@article{ad99b0e73a304b16948b19db05380415,
title = "Correction of the enzymic defect in cultured fibroblasts from patients with Fabry's disease: Treatment with purified α galactosidase from ficin",
abstract = "Cultured skin fibroblasts from patients with Fabry's disease showed the characteristic α galactosidase deficiency and accumulated a four- to sixfold excess of trihexosylceramide (GL-3). To demonstrate the correction, cells previously labeled with U 14C glucose were grown in medium containing a purified α galactosidase preparation obtained from ficin. The results demonstrated that α galactosidase was taken up rapidly from the medium and that, despite its apparent instability in the fibroblasts, it was able to become incorporated into lysosomes and catabolize the stored trihexosylceramide. These findings support the reports of therapeutic endeavors by renal transplantation and plasma infusion in Fabry's disease and suggest the extension of such studies to other related disorders in which the cultured skin fibroblasts are chemically abnormal, namely, Gaucher's disease, lactosylceramidosis, and G(M2) gangliosidosis type II. It may be possible to replace the specific missing lysosomal hydrolase in various spingolipidoses and other storage diseases. Although the authors do not propose to effect enzyme replacement therapy in vivo with a plant enzyme, such studies in tissue culture are valid, and eventually human α galactosidase, of comparable activity and purity, will become available.",
author = "G. Dawson and Reuben Matalon and {Yu Teh Li}, {Teh Li}",
year = "1973",
language = "English (US)",
volume = "7",
pages = "684--690",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Correction of the enzymic defect in cultured fibroblasts from patients with Fabry's disease

T2 - Treatment with purified α galactosidase from ficin

AU - Dawson, G.

AU - Matalon, Reuben

AU - Yu Teh Li, Teh Li

PY - 1973

Y1 - 1973

N2 - Cultured skin fibroblasts from patients with Fabry's disease showed the characteristic α galactosidase deficiency and accumulated a four- to sixfold excess of trihexosylceramide (GL-3). To demonstrate the correction, cells previously labeled with U 14C glucose were grown in medium containing a purified α galactosidase preparation obtained from ficin. The results demonstrated that α galactosidase was taken up rapidly from the medium and that, despite its apparent instability in the fibroblasts, it was able to become incorporated into lysosomes and catabolize the stored trihexosylceramide. These findings support the reports of therapeutic endeavors by renal transplantation and plasma infusion in Fabry's disease and suggest the extension of such studies to other related disorders in which the cultured skin fibroblasts are chemically abnormal, namely, Gaucher's disease, lactosylceramidosis, and G(M2) gangliosidosis type II. It may be possible to replace the specific missing lysosomal hydrolase in various spingolipidoses and other storage diseases. Although the authors do not propose to effect enzyme replacement therapy in vivo with a plant enzyme, such studies in tissue culture are valid, and eventually human α galactosidase, of comparable activity and purity, will become available.

AB - Cultured skin fibroblasts from patients with Fabry's disease showed the characteristic α galactosidase deficiency and accumulated a four- to sixfold excess of trihexosylceramide (GL-3). To demonstrate the correction, cells previously labeled with U 14C glucose were grown in medium containing a purified α galactosidase preparation obtained from ficin. The results demonstrated that α galactosidase was taken up rapidly from the medium and that, despite its apparent instability in the fibroblasts, it was able to become incorporated into lysosomes and catabolize the stored trihexosylceramide. These findings support the reports of therapeutic endeavors by renal transplantation and plasma infusion in Fabry's disease and suggest the extension of such studies to other related disorders in which the cultured skin fibroblasts are chemically abnormal, namely, Gaucher's disease, lactosylceramidosis, and G(M2) gangliosidosis type II. It may be possible to replace the specific missing lysosomal hydrolase in various spingolipidoses and other storage diseases. Although the authors do not propose to effect enzyme replacement therapy in vivo with a plant enzyme, such studies in tissue culture are valid, and eventually human α galactosidase, of comparable activity and purity, will become available.

UR - http://www.scopus.com/inward/record.url?scp=0015877842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0015877842&partnerID=8YFLogxK

M3 - Article

C2 - 4732107

AN - SCOPUS:0015877842

VL - 7

SP - 684

EP - 690

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 8

ER -