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

✍ Scribed by Steven E. Brooks; Linda M. Hoffman; Daniel Amsterdam; Masazumi Adachi; Larry Schneck

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 493 KB
• Volume: 6
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490060313

✦ Synopsis

Abstract

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.