Enzyme replacement treatment for Tay-Sachs disease brain cells in culture utilizing Concanavalin A-mediated hexosaminidase A uptake: Biochemical and morphological evidence of GM2 mobilization

Publisher Website
Google Scholar
Abstract
When Concanavalin A (Con A) is bound to the cell membrane, it functions as an artificial enzyme receptor, mediating the binding and intracellular incorporation of significant amounts of exogenous hexosaminidase A (Hex A) into Tay-Sachs disease (TSD) glial cells. The treated cells retained almost 50% of incorporated Hex A activity after 3 days incubation in Hex A free medium. Hex A was released from Con A within the cell and was available as free enzyme. Biochemical analysis of gangliosides in Con A and Hex A treated cells depicted a greater than 50% reduction in stored GM2 ganglioside and a fourfold reduction in GM2label (14C) when compared to controls. Ultrastructural evidence of GM2 breakdown is presented which supports the biochemical and labeling studies.