Cocaine hydrolase gene transfer demonstrates cardiac safety and efficacy against cocaine-induced QT prolongation in mice

Vishakantha Murthy, Santiago Reyes, Liyi Geng, Yang Gao, Stephen Brimijoin

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Cocaine addiction is associated with devastating medical consequences, including cardiotoxicity and risk-conferring prolongation of the QT interval. Viral gene transfer of cocaine hydrolase engineered from butyrylcholinesterase offers therapeutic promise for treatment-seeking drug users. Although previous preclinical studies have demonstrated benefits of this strategy without signs of toxicity, the specific cardiac safety and efficacy of engineered butyrylcholinesterase viral delivery remains unknown. Here, telemetric recording of electrocardiograms from awake, unrestrained mice receiving a course of moderately large cocaine doses (30 mg/kg, twice daily for 3 weeks) revealed protection against a 2-fold prolongation of the QT interval conferred by pretreatment with cocaine hydrolase vector. By itself, this prophylactic treatment did not affect QT interval duration or cardiac structure, demonstrating that viral delivery of cocaine hydrolase has no intrinsic cardiac toxicity and, on the contrary, actively protects against cocaine-induced QT prolongation.

Original languageEnglish (US)
Pages (from-to)720-725
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume356
Issue number3
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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