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

Gene Therapy volume 7, pages 2094–2098 (2000)Cite this article

Abstract

Adenovirus-mediated gene transfer of interferon gamma (AdIFN) 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 AdIFN or β-galactosidase adenovirus (AdBGAL) perform as well as non-injected animals in behavioral, memory, and motor tests. Both AdIFN and AdBGAL elicit demyelination whose incidence rises sharply when the lowest effective dose of AdIFN 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.

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Acknowledgements

This work was supported by grants from the National Cancer Institute (R01-CA81367 and R29-CA78825 to HM Fathallah-Shaykh). Statistical analysis was supported by the Simmons Cancer Center at the University of Texas Southwestern Medical Center at Dallas. We are grateful to Roger Rosenberg for discussions and encouragement. We would also like to acknowledge the support of Mr Theodore Strauss and the Annette Strauss Center for Neuro-Oncology at UT Southwestern Medical Center.

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Authors and Affiliations

  1. Department of Neurology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    H M Fathallah-Shaykh, A I Kafrouni, L-J Zhao & R Diaz-Arrastia

  2. Department of Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    J A Garcia

  3. Department of Academic Computing Services, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    W H Frawley

  4. The University of Texas Southwestern Medical Center at Dallas, Center For Immunology, Dallas, TX, USA

    J Forman

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  1. H M Fathallah-Shaykh
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Fathallah-Shaykh, H., Kafrouni, A., Zhao, LJ. et al. Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain. Gene Ther 7, 2094–2098 (2000). https://doi.org/10.1038/sj.gt.3301346

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Keywords

  • brain
  • gene therapy
  • adenovirus
  • interferon gamma
  • behavior

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