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Long-term correction of rat model of Parkinson's disease by gene therapy

A Retraction to this article was published on 25 April 1996

Abstract

THE implantation of cells genetically modified to express tyrosine hydroxylase has been proposed for the treatment of Parkinson's disease1. Tyrosine hydroxylase converts tyrosine to L-DOPA and endogenous decarboxylase activity then converts L-DOPA to the neurotransmitter dopamine, which alleviates the symptoms of Parkinson's disease. Immortalized cells have been successfully used as intracerebral vehicles for transgene expression of tyrosine hydroxylase, but the tumorigenic potential of these cells prevents their application in humans1–4. Intracerebral expression of this enzyme has also been achieved using primary cells like skin fibroblasts5–7, but the ameliorating effect on a rat model for Parkinson's disease lasted for only a few weeks. We have found that co-transplantation of cultured myoblasts and myotubes enabled reporter genes to be expressed intracerebrally at high and stable levels8–10. Here we show that the intracerebral transplantation of plasmid-transfected primary muscle cells can substantially reduce for the long-term the asymmetric rotational behaviour in the rat model.

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References

  1. Wolff, J. A. et al. Proc. natn. Acad Sci. U.S.A. 86, 9011–9014 (1989).

    Article  ADS  CAS  Google Scholar 

  2. Horellou, P. et al. Neuron. 5, 393–402 (1990).

    Article  CAS  Google Scholar 

  3. Stromberg, I. et al. J. Neurosci. Res. 25, 405–411 (1990).

    Article  CAS  Google Scholar 

  4. Gage, F. H. et al. Neuroscience 23, 795–807 (1987).

    Article  CAS  Google Scholar 

  5. Gage, F. H. & Fisher, L. J. et al. Neuron 6, 1–12 (1991).

    Article  CAS  Google Scholar 

  6. Fisher, L. J. et al. Neuron 6, 371–380 (1991).

    Article  CAS  Google Scholar 

  7. Chen, L. S. et al. J. cell. Biochem. 45, 252–257 (1991).

    Article  CAS  Google Scholar 

  8. Jiao, S. S., Schultz, E. & Wolff, J. A. Brain Res. 575, 143–147 (1992).

    Article  CAS  Google Scholar 

  9. Jiao, S. S. et al. Cell Transpl. (in the press).

  10. Jiao, S. S. & Wolff, J. A. Neurosci. Lett. 137, 207–210 (1992).

    Article  CAS  Google Scholar 

  11. Wolff et al. Hum. Molec. Genet. 1, 363–369 (1992).

    Article  CAS  Google Scholar 

  12. Dan, Y. & Poo, M. Nature 359, 733–736 (1992).

    Article  ADS  CAS  Google Scholar 

  13. Birkmayer, G. J. D. & Birkmayer, W. Acta neurol Scand. 126, 183–187 (1989).

    Article  CAS  Google Scholar 

  14. Kapatos, G., Katoh, S. & Kaufman, S. J. Neurochem. 39, 1152–1162 (1982).

    Article  CAS  Google Scholar 

  15. Wakai, S., Meiselman, S. E. & Brightman, M. W. Brain Res. 386, 209–222 (1986).

    Article  CAS  Google Scholar 

  16. Palmer, T. D., Rosman, G. Y., Osborne, W. R. A. & Miller, A. D. Proc. natn. Acad. Sci. U.S.A. 88, 1330–1334 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Melamed, E. in Handbook of Parkinson's Disease (ed. Koller, W. C.) 355–370 (Dekker, New York, 1987).

    Google Scholar 

  18. Kamahori, M., Taki, M. & Watanabe, Y. J. J. Chromat. 567, 351–358 (1991).

    Article  CAS  Google Scholar 

  19. Crombeen, J. P., Kraak, J. C. & Poppe, H. J. Chromat. 167, 219–230 (1978).

    Article  CAS  Google Scholar 

  20. Svendsen, H. & Greibrokk, T. J. Chromat. 213, 429–437 (1981).

    Article  CAS  Google Scholar 

  21. Norton, P. A. & Coffin, J. M. Molec. cell. Biol. 5, 281–290 (1985).

    Article  CAS  Google Scholar 

  22. Brown, E. R., Coker, G. T. T. & O'Malley, K. L. Biochemistry 26, 5208–5212 (1987).

    Article  CAS  Google Scholar 

  23. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic, New York, 1982).

    Google Scholar 

  24. Perlow, M. J. et al. Science 204, 643–647 (1979).

    Article  ADS  CAS  Google Scholar 

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Jiao, S., Gurevich, V. & Wolff, J. Long-term correction of rat model of Parkinson's disease by gene therapy. Nature 362, 450–453 (1993). https://doi.org/10.1038/362450a0

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