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Gene therapy of Parkinson’s disease using Adeno-Associated Virus (AAV) vectors

  • K. Ozawa
  • D.-S. Fan
  • Y. Shen
  • S. Muramatsu
  • K. Fujimoto
  • K. Ikeguchi
  • M. Ogawa
  • M. Urabe
  • A. Kume
  • I. Nakano
Conference paper

Summary

Parkinson’s disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene theraphy of PD is instratiatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)]. The most appropiate gene-delivery vehicles for neurons are adeno-associated virus (AAV) vectors, which are derived from non-pathogenic virus. Therefore, TH and AADC genes were introduced into the striatum in the lesioned side using separate AAV vectors in parkinsonian rats, and the coexpression of TH and AADC resulted in better behavorial recovery compared with TH alone. Another strategy for gene therapy of PD is the protection of dopaminergic neurons in the substantia nigra using an AAV vector containing a glial cell line-derived neurotrophic factor (GDNF) gene. Combination of dopamine-supplement gene therapy and GDNF gene therapy would be a logical approach to the treatment of PD.

Keywords

Gene Therapy Tyrosine Hydroxylase Dopaminergic Neuron Striatal Cell Human Tyrosine Hydroxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • K. Ozawa
    • 1
  • D.-S. Fan
    • 1
    • 2
  • Y. Shen
    • 1
    • 2
  • S. Muramatsu
    • 2
  • K. Fujimoto
    • 2
  • K. Ikeguchi
    • 2
  • M. Ogawa
    • 2
  • M. Urabe
    • 1
  • A. Kume
    • 1
  • I. Nakano
    • 2
  1. 1.Division of Genetic Therapeutics, Center for Molecular MedicineJichi Medical SchoolMinamikawachi-machi, Kawachi-gun, TochigiJapan
  2. 2.Department of NeurologyJichi Medical SchoolTochigiJapan

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