Adenovirus-Mediated th Gene Therapy
of Parkinson’s Disease in a Experimental Rat Model
XU De-Hua*, XU Lin-Fei, SHI Chang-Gen, ZHUO Ming,
CAO Lei, LIU Xin-Yuan, ZHENG Zhong-Cheng
( Shanghai Institute of Biochemistry, the Chinese Academy of Sciences,
Shanghai 200031, China )
Abstract 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 1.4×1014 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 1×106 AdCMV th
infected glial cells, but no detectable DA was found in AdCMVLacZ-infected
glial cells. Injection of AdCMV th (1×107 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.
Key words Parkinson’s disease； gene therapy； th gene； adenovirus； rat
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