Abstract
A genetic neurodegenerative disorder with lysosomal storage of Gm2 ganglioside, its asialo derivative, and globoside, and β-hexosaminidase deficiency has been described in domestic cats (Cork et al, Science, 1977, in press). To strengthen the apparent analogy with human Gm2 gangliosidosis type II, feline β-hexosaminidase has been studied. Two major forms of this lysosomal enzyme, Hex A and Hex B, are present in organs and body fluids from normal animals, with biochemical and kinetic properties remarkably similar to those of the corresponding human enzymes. These data, and the deficiency of both components in affected cats, support the analogy between feline and human diseases. Thus it is possible to utilize this animal model for enzyme therapy experiments. Structural differences between human and feline β-hexosaminidase, however, may result in different cellular uptake, endocellular activity and stability, limiting the relevance of replacement experiments with feline enzyme. Thus, plasma clearance and organ disposition of human placental Hex A and Hex B has been studied in normal cats, utilizing the apparent absence of interspecific immunologic cross-reactivity. The results so far indicate a rapid, preferential hepatic uptake, possibly via a saturable receptor mechanism, with recovery of the exogenous enzymes in a lysosomal fraction. Further studies using human enzymes should result in enzyme replacement strategies, to be tested in diseased cats, relevant to therapeutic attempts in human Gm2 gangliosidosis.
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Rattazzi, M. THE CAT AS A MODEL FOB ENZYME THERAPY IN GM2 GANGLIOSIDOSIS. Pediatr Res 11, 462 (1977). https://doi.org/10.1203/00006450-197704000-00555
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DOI: https://doi.org/10.1203/00006450-197704000-00555