Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

Gene Therapy
James GossDavid J Fink

Abstract

Endogenous opiate peptides acting pre- and post-synaptically in the dorsal horn of spinal cord inhibit transmission of nociceptive stimuli. We transfected neurons of the dorsal root ganglion in vivo by footpad inoculation with 30 microl (3 x 10(7) p.f.u.) of a replication-incompetent (ICP4-deleted) herpes simplex virus (HSV) vector with a cassette containing a portion of the human proenkephalin gene coding for 5 met- and 1 leu-enkephalin molecules under the control of the human cytomegalovirus immediate-early promoter (HCMV IEp) inserted in the HSV thymidine kinase (tk) locus. Vector-directed expression of enkephalin produced a significant antinociceptive effect measured by the formalin footpad test, that was most prominent in the delayed ("tonic") phase 20-70 min after the administration of formalin. The magnitude of the antinociceptive effect diminished over 4 weeks after transduction, but reinoculation of the vector reestablished the analgesic effect, without evidence for the development of tolerance. The antinociceptive effect was blocked completely by intrathecal naltrexone. These results suggest that gene therapy with an enkephalin-producing herpes-based vector may prove useful in the treatment of pain.

Associated Clinical Trials

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Citations

Oct 29, 2002·Annals of Neurology·James R GossDavid J Fink
Jun 27, 2007·Biotechnology and Bioengineering·James B WechuckMohammad M Ataai
Dec 20, 2003·Current Neurology and Neuroscience Reports·Marina MataDavid J Fink
Feb 11, 2004·Experimental Neurology·Atsushi NatsumeMarina Mata
Nov 5, 2003·Experimental Neurology·Marina MataDavid J Fink
Jan 16, 2003·Physiology & Behavior·Marina MataDavid J Fink
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Oct 9, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Joseph C Glorioso, David J Fink
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Jun 27, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Munmun ChattopadhyayDavid J Fink
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Mar 31, 2012·Pain Management·David J Fink, Darren Wolfe
Feb 8, 2014·Human Gene Therapy·Joseph C Glorioso
May 12, 2007·Expert Review of Neurotherapeutics·James R GossJoseph C Glorioso

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