Long-term intracellular retention of hexosaminidase A by Tay-Sachs disease brain and lung cells in vitro.

Enzyme-replacement treatment for metabolic storage disorders has been widely studied using model cell culture systems. This study determines the long-term fate of human hexosaminidase A supplied to Tay-Sachs disease brain and lung cells. Hex A retention studies showed that the incorporated Hex A is retained in undiminished quantity by TSD lung cells maintained in stationary culture for 14 days. Tay-Sachs disease brain cells similarly followed for 28 days in stationary culture showed an initial reduction in Hex A for 3 days, after which the Hex A level stabilized and remained relatively constant for the next 25 days. Hexosaminidase B isoenzyme was found to accumulate in both cell lines during extended cultivation, despite the observation that significant amounts were excreted into the extracellular environment. The demonstration of long-term intracellular retention of exogenously supplied therapeutic enzyme by the target cells offers additional evidence for the feasibility of an enzyme-replacement approach for study and treatment of lysosomal storage disorders.