Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain

H. M. Fathallah-Shaykh, A. I. Kafrouni, L. J. Zhao, R. Diaz-Arrastia, J. A. Garcia, W. H. Frawley, J. Forman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Adenovirus-mediated gene transfer of interferon gamma (AdlFN) elicits rejection of intracerebral Lewis lung carcinoma. In this system, gene transfer into brain parenchymal cells is both necessary and sufficient to generate the antitumor response. Despite persistent parenchymal inflammation and demyelination, wild-type mice injected intracerebrally with either AdlFN or β-galactosidase adenovirus (AdBGAL) perform as well as non-injected animals in behavioral, memory, and motor tests. Both AdlFN and AdBGAL elicit demyelination whose incidence rises sharply when the lowest effective dose of AdlFN is exceeded. Therefore, transfer of interferon gamma into brain parenchyma does not seem to elicit detectable cognitive, behavioral or motor deficits. Furthermore, gene transfer into the brain, by adenoviral vectors currently in clinical trials, is associated with a narrow therapeutic window where the incidence of demyelination rises sharply soon after the effective dose is achieved.

Original languageEnglish (US)
Pages (from-to)2094-2098
Number of pages5
JournalGene Therapy
Volume7
Issue number24
DOIs
StatePublished - 2000

Fingerprint

Demyelinating Diseases
Adenoviridae
Brain
Genes
Interferon-gamma
Galactosidases
Lewis Lung Carcinoma
Incidence
Clinical Trials
Inflammation
Transfer (Psychology)
Therapeutics

Keywords

  • Adenovirus
  • Behavior
  • Brain
  • Gene therapy
  • Interferon gamma

ASJC Scopus subject areas

  • Genetics

Cite this

Fathallah-Shaykh, H. M., Kafrouni, A. I., Zhao, L. J., Diaz-Arrastia, R., Garcia, J. A., Frawley, W. H., & Forman, J. (2000). Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain. Gene Therapy, 7(24), 2094-2098. https://doi.org/10.1038/sj.gt.3301346

Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain. / Fathallah-Shaykh, H. M.; Kafrouni, A. I.; Zhao, L. J.; Diaz-Arrastia, R.; Garcia, J. A.; Frawley, W. H.; Forman, J.

In: Gene Therapy, Vol. 7, No. 24, 2000, p. 2094-2098.

Research output: Contribution to journalArticle

Fathallah-Shaykh, HM, Kafrouni, AI, Zhao, LJ, Diaz-Arrastia, R, Garcia, JA, Frawley, WH & Forman, J 2000, 'Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain', Gene Therapy, vol. 7, no. 24, pp. 2094-2098. https://doi.org/10.1038/sj.gt.3301346
Fathallah-Shaykh HM, Kafrouni AI, Zhao LJ, Diaz-Arrastia R, Garcia JA, Frawley WH et al. Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain. Gene Therapy. 2000;7(24):2094-2098. https://doi.org/10.1038/sj.gt.3301346
Fathallah-Shaykh, H. M. ; Kafrouni, A. I. ; Zhao, L. J. ; Diaz-Arrastia, R. ; Garcia, J. A. ; Frawley, W. H. ; Forman, J. / Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain. In: Gene Therapy. 2000 ; Vol. 7, No. 24. pp. 2094-2098.
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