Adenovirus-mediated gene therapy for experimental spinal cord tumors: tumoricidal efficacy and functional outcome

Ahmet Çolak, J. Clay Goodman, Shu Hsia Chen, Savio L C Woo, Robert G. Grossman, H. David Shine

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

We evaluated the efficacy of adenoviral-mediated gene therapy of experimental spinal cord tumors and the functional outcome after this treatment. Spinal cord tumors were generated in the thoracic region of the spinal cord in Fischer 344 rats by stereotaxic intramedullary injection of 1 × 104 9L gliosarcoma cells. Seven days after tumor cell injection, a replication-defective adenoviral vector carrying the herpes simplex virus thymidine kinase gene (ADV-tk) or a control adenoviral vector carrying the β-galactosidase gene (ADV-βgal) was injected into the tumors. Beginning 12 h later the animals were treated with the antiviral drug ganciclovir (GCV; 50 mg/kg) or saline twice a day for 6 days. The neurological performance of the animals was assessed during and following treatment. Eighteen days after tumor cell injection, all of the control animals had paraplegia and large tumors. In contrast, no tumors were detected in animals treated with ADV-tk and GCV. In long-term studies, two of the 5 animals treated with ADV-tk and GCV remained tumor-free and remained neurologically intact at 6 months whereas all animals in the control groups became paraplegic within 18 days.

Original languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalBrain Research
Volume691
Issue number1-2
DOIs
StatePublished - Sep 11 1995

Keywords

  • Adenovirus
  • Gene therapy
  • Herpes simplex virus
  • Spinal cord tumor
  • Thymidine kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology
  • Developmental Biology

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