Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinsonʼs disease

DIRECT intracerebral gene transfer to neural cells has been demonstrated with recombinant adenovirus encoding β-galactosidase. To explore the potential of recombinant adenovirus for the therapy of neurological disease we constructed a recombinant adenovirus encoding tyrosine hydroxylase, and optimized intracerebral injection to express the gene in the striatum of unilaterally denervated rats. These animals have dopamine depletion in their lesioned striatum, causing a rotation asymmetry induced by apomorphine. One, and two weeks after intracerebral injection this sensorimotor asymmetry was decreased by the adenovirus encoding tyrosine hydroxylase, and not by a control adenovirus encoding β-galactosidase. Histological analysis showed that tyrosine hydroxylase was preferentially expressed in astrocytes.