Continuous DOPA synthesis from a single AAV: Dosing and efficacy in models of Parkinson's disease

Erik Cederfjäll, Nathalie Nilsson, Gurdal Sahin, Yaping Chu, Elisabeth Nikitidou, Tomas Björklund, Jeffrey H. Kordower, Deniz Kirik

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


We used a single adeno-associated viral (AAV) vector co-expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) to investigate the relationship between vector dose, and the magnitude and rate of recovery in hemi-parkinsonian rats. Intrastriatal injections of >1E10 genomic copies (gc) of TH-GCH1 vector resulted in complete recovery in drug-naïve behavior tests. Lower vector dose gave partial to no functional improvement. Stereological quantification revealed no striatal NeuN+ cell loss in any of the groups, whereas a TH-GCH1 dose of >1E11 gc resulted in cell loss in globus pallidus. Thus, a TH-GCH1 dose of 1E10 gc gave complete recovery without causing neuronal loss. Safety and efficacy was also studied in non-human primates where the control vector resulted in co-expression of the transgenes in caudate-putamen. In the TH-GCH1 group, GCH1 expression was robust but TH was not detectable. Moreover, TH-GCH1 treatment did not result in functional improvement in non-human primates.

Original languageEnglish (US)
Article number2157
JournalScientific reports
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • General


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