Reparative strategies in the brain: treatment strategies based on trophic factors and cell transfer techniques

Three reparative strategies based on transfer of genes, molecules, or cells to the central nervous system are reviewed. When neurons are already lost, they can sometimes be replaced by transfer to the target area of neurons or other cells compensating for the lost functions. This technique is undergoing clinical trials in Parkinson's disease. Before neurons have died, it may be possible to prevent "stressed" neurons from dying, and stimulate nerve terminal ramifications from remaining neurons using treatment with neurotrophic factors. Such approaches, with an emphasis on the NGF family of neurotrophins and their receptors, are reviewed. Finally, advances of molecular biology techniques suggest that it should be possible to transfer genes directly into non-dividing cells of the central nervous system. The three different approaches all aim at long-lasting counteractive and reparative measures in the central nervous system. It is predicted that they have general applicability, and may become important not only in neurodegenerative diseases, but also in other common afflictions of the nervous system such as ischaemia, stroke and injury.