[Gene therapy in neurology. State of the art and future prospects]

Some 100 neurological disorders are known today to have a genetic cause. Most involve severe dysfunction and are not candidates for conventional therapies. Recent conceptual and methodological advances, however, allow for therapeutic approaches that substitute defective genes for functioning equivalents, through what we now call "gene therapy". New pathways are thus open for treatment. Two major strategies have been proposed for gene transference, one physical and the other biological, each with inherent advantages and limitations. Herpes simplex virus is, a priori, an ideal vector as a consequence of its trophic relation to cells of the nervous system and in fact this virus has been applied repeatedly in animal models of gene therapy. The toxicity of herpes simplex infections, however, and our ignorance of their effect on the receptor genome, have put constraints on its use in humans. Retroviruses have also been tested in treatment protocols for malignant brain tumors in humans. Other strategies involve genetic modification of cultivated cells in vitro for subsequent implantation in the appropriate tissue for ongoing production of neurotrophic factors or growth. We describe the various strategies for gene transference and evaluate the results obtained.