EX-VIVO GENE-THERAPY FOR ALZHEIMERS-DISEASE AND SPINAL-CORD INJURY

Gene transfer is a potential means of treating chronic neurologic diso rders and injury related neural degeneration. One approach for transfe ring genes to the CNS is to genetically modify cells in vitro and then transplant the cells to the CNS. For example, fibroblasts can be infe cted with a replication-defective retrovirus expressing a transgene, a nd can then be transplanted into the brain or spinal cord, thereby pro viding neurotrophic factors and substrates for axonal growth and elong ation. In this review we discuss the grafting of neurotrophic factor s ecreting autologous fibroblasts in the rat and primate CNS. NGF secret ing grafts have been shown to prevent degeneration of cholinergic neur ons in the basal forebrain of primates and to induce sprouting of sens ory motor, and noradrenergic neurites after spinal cord injury. These results suggest the potential usefulness of ex vivo gene transfer for the treatment of Alzheimer's disease and spinal cord injury. (C) 1996 Wiley-Liss, Inc.