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 GM2-gangliosidosis type II. It may be possible to replace the specific missing lysosomal hydrolase in various sphingolipidoses and other storage diseases. Although we 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. © 1973 International Pediatric Research Foundation, Inc.