Readministration of adenoviral gene delivery to dopamine neurons.

An approach currently being explored as treatment for Parkinson's disease is gene therapy. An important question concerns the duration of transgene expression in dopamine neurons and the issues of vector persistence, neuronal damage and the feasibility of readministering vector to the same neuronal population. We show, using an adenoviral vector expressing the LacZ reporter gene, that transgene expression declined over time but with minimal loss of dopamine neurons or vector DNA.

Neuropathological consequences of delivering an adenoviral vector in the rat brain.

Background: Adenoviruses have many advantages as vehicles for gene delivery to the central nervous system (CNS) and retrograde transport of vectors to axonally linked sites has been postulated as a method for targeting neurons in remote brain regions. To investigate optimisation of this we injected different doses of vector and have documented the neuropathological side effects.

Methods: Increasing doses of a first-generation adenoviral vector, expressing the lacZ gene, were inoculated in the rat striatum and beta-galactosidase expression was examined at the primary and secondary sites.