Gene therapy to prevent organophosphate intoxication

J. Cowan, C. M. Sinton, A. W. Varley, F. H. Wians, R. W. Haley, R. S. Munford

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The specific hydrolytic activity of PON1 paraoxonase/arylesterase enzymes in liver and blood provides a natural barrier against the entry of organophosphate toxins into the central and peripheral nervous systems. Inherited differences in PON1 enzyme concentrations may determine levels of susceptibility to organophosphate injury in humans. To test whether boosting serum levels of PON1 enzymes by gene therapy might provide increased protection, we compared the degree of inactivation of whole brain acetylcholinesterase of mice exposed to chlorpyrifos 4 days after intravenous injection of recombinant adenoviruses containing PON1-LQ or PON1-LR genes or no PON1 gene. Both recombinant viruses containing PON1 genes boosted serum arylesterase concentrations by approximately 60% and significantly prevented the inactivation of brain acetylcholinesterase. Some mice were completely protected. These findings indicate that boosting serum levels of PON1 enzymes by a gene delivery vector raises the threshold for organophosphate toxicity by hydrolytic destruction before the chemical can enter the brain.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalToxicology and Applied Pharmacology
Volume173
Issue number1
DOIs
StatePublished - May 15 2001

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Gene therapy to prevent organophosphate intoxication'. Together they form a unique fingerprint.

  • Cite this

    Cowan, J., Sinton, C. M., Varley, A. W., Wians, F. H., Haley, R. W., & Munford, R. S. (2001). Gene therapy to prevent organophosphate intoxication. Toxicology and Applied Pharmacology, 173(1), 1-6. https://doi.org/10.1006/taap.2001.9169