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Long‐term intracellular retention of hexosaminidase A by Tay‐Sachs disease brain and lung cells in vitro
Author(s) -
Brooks Steven E.,
Hoffman Linda M.,
Amsterdam Daniel,
Adachi Masazumi,
Schneck Larry
Publication year - 1981
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490060313
Subject(s) - intracellular , tay sachs disease , enzyme , in vitro , hexosaminidase , extracellular , cell culture , cell , biology , enzyme replacement therapy , lung , enzyme assay , biochemistry , chemistry , medicine , microbiology and biotechnology , disease , genetics
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.