Gene therapy of neurological disorders. Experimental paradigms and clinical perspectives

Abstract

So far, it has not been possible to treat many neurological conditions causally. However, in the past few years underlying genetic defects have been characterized for a substantial number of neurodegenerative disorders. Experimental methods have been developed that allow for efficient gene transfer into defined regions of the mammalian CNS. Such techniques can be applied to deliver genes into target cells of a recipient organism or to transfer genetically modified cells into defined regions of the CNS. Candidate genes for gene therapy are those encoding for neurotrophins and neurotransmitters for symptomatic therapy and, in the case of neurodegenerative disorders with localized gene defects, the wild-type allele as a causal treatment approach. In this review article, we describe some of the most widely used strategies for gene transfer to the CNS. We also report on the results obtained with animal models for human disease, and discuss both the chances and problems of gene therapy approaches in clinical medicine.