Neuronal grafting into the CNS has recently been suggested as a potential approach to CNS therapy through the selective replacement of cells lost as a function of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic diseases, especially those caused by single gene deficiencies. We have recently suggested that a combination of these two approaches, namely the grafting into the CNS. We have presented evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting. In this application we propose to test the phenotypic effects of implanting cells expressing on of 2 vitally transduced genes - the E. coli B-galactosidase (ladZ gene product) to optimize conditions for grafting, and mouse Nerve Growth Factor (NGF) to establish a phenotypic effect in young animals with brain damage, or aged animals with morphological and cognitive deficits.
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