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

Abstract

Direct intracerebral gene transfer to neural cells has been demonstrated with recombinant adenovirus encoding beta-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 beta-galactosidase. Histological analysis showed that tyrosine hydroxylase was preferentially expressed in astrocytes.