Gene transfer into the central nervous system (CNS) is one of the foremost
scientific challenges today. To give a brief survey of possible approaches
to gene therapy in diseases affecting the CNS, we have selected the lysosom
al storage diseases (LDS), which are an excellent model of both early-onset
infantile neurological forms and late-onset adult psychiatric forms. Lysos
omal storage diseases represent a group of about 50 monogenic metabolic dis
orders resulting from a deficiency in intralysosomal enzymes involved in ma
cromolecule catabolism. The clinical severity, including neuropsychiatric s
ymptoms, and the absence of an efficient therapy for the majority of these
disorders prompted the various trials of gene therapy now in progress. Most
of the genes encoding the normal lysosomal enzymes have been cloned. and t
he size of the corresponding cDNAs is generally compatible with their trans
fer by recombinant vectors. New vectors with improved immunogenicity, trans
duction efficacy, insert capacity, and specificity of targeting are under d
evelopment. Here we discuss several gene therapy strategies for the correct
ion of LSD-induced anomalies in the CNS. Interesting results have been obta
ined by animal model brain, which raises hopes that large-scale clinical tr
ials may soon be started.