Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson's disease

Neuroscience. 1999;92(1):185-96. doi: 10.1016/s0306-4522(98)00741-6.


As a potential treatment for Parkinson's disease, viral vector-mediated over-expression of striatal L-aromatic amino acid decarboxylase was tested in an attempt to facilitate the production of therapeutic levels of dopamine after peripheral L-dihydroxyphenylalanine administration. The results of microdialysis and enzyme activity assays indicate that striatal decarboxylation of peripherally administered L-dihydroxyphenylalanine was enhanced by recombinant adeno-associated virus-mediated gene transfer of L-aromatic amino acid decarboxylase in unilateral 6-hydroxydopamine-lesioned rats. This gene transfer-induced increase in striatal decarboxylase activity was shown to remain undiminished over a six-month period and transgene expression was demonstrated to persist for at least one year. Unlike previous approaches involving delivery of either tyrosine hydroxylase, or tyrosine hydroxylase and L-aromatic amino acid decarboxylase transgenes together to accomplish unregulated dopamine delivery, the current study proposes a pro-drug strategy (peripheral L-dihydroxyphenylalanine administration after L-aromatic amino acid decarboxylase transduction). This strategy for dosage control could potentially allow lowered L-dihydroxyphenylalanine doses and potentially obviate complicated transcriptional regulation paradigms. These data suggest that the use of the non-pathogenic adeno-associated virus to transfer the L-aromatic amino acid decarboxylase gene into the striatum of Parkinson's disease patients may be an attractive gene therapy strategy.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / genetics*
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Corpus Striatum / enzymology*
  • Dopamine / biosynthesis
  • Gene Expression / physiology
  • Gene Transfer Techniques*
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Male
  • Parkinson Disease / enzymology*
  • Rats
  • Rats, Inbred F344
  • Recombination, Genetic
  • Time Factors
  • Transduction, Genetic / physiology


  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine