Adenovirus-Mediated th Gene Therapy of Parkinson's Disease in a Experimental Rat Model.
A recombinant adenovirus (AdCMV th) encoding tyrosine hydroxylase (TH) gene with CMV promoter was constructed and propagated. Southern blot analyses was used to identify positive plaques. Virus titer was about 1.4x10(14) pfu/L as determined by plaque forming assay. In glial cells infected with AdCMV th, the TH expression was demonstrated by immunohistochemical staining and HPLC-ECD. 678.8 ng DA was detected in the extract of 1x10(6) AdCMV th infected glial cells, but no detectable DA was found in AdCMVLacZ-infected glial cells. Injection of AdCMV th (1x10(7) pfu/rat) into the striatum of PD rats significantly improved the apomorphine-induced rotation movement(approximately 60%). The improvement in rotation movement remained up to 5 months after injection, and TH expression positive cells were found in the vicinity of injection. These results indicate that adenovirus may be a useful carrier for in vivo gene therapy in the PD patients.
Xu
De-Hua
DH
Shanghai Institute of Biochemistry, the Chinese Academy of Sciences, Shanghai 200031, China. sib203@sunm.shcnc.ac.cn
Xu
Lin-Fei
LF
Shi
Chang-Gen
CG
Zhuo
Ming
M
Cao
Lei
L
Liu
Xin-Yuan
XY
Zheng
Zhong-Cheng
ZC