Prospects for gene therapy in pediatric neurosurgery.

Gene therapy represents a powerful tool for both the study and potential treatment of pediatric neurological diseases. The majority of strategies for brain gene therapy have focused upon the use of modified viruses as vehicles for efficient delivery of genes into cells of the central nervous system. Retroviruses were originally the most popular vehicles for gene transfer outside the brain; however, these only function in actively dividing cells and have thus been limited to developmental neurobiology and treatment of brain tumors. Viruses with DNA-based genomes can transfer genes to both dividing and nondividing cells such as neurons, and these include adenovirus, adeno-associated virus and herpes simplex virus. Each system has special features, and the choice of vehicle may be based upon a variety of factors including toxicity or immunogenicity of the vector in vivo, size of the gene which can be inserted, titer of virus which can be obtained and technical difficulty in generating reagent grade viruses. Pediatric patients present unique opportunities for gene therapy, and inherited genetic defects and brain tumors are among the pediatric disorders which would most benefit from this new field. Preclinical studies using each of these systems in a variety of models of pediatric CNS disease have proven promising. Several ongoing studies have been initiated for treatment of pediatric brain tumors, and a protocol for treatment of an inherited neurological defect has recently achieved approval for initial clinical trials. Continued advances in gene therapy technology and delivery systems combined with the explosion of available genetic information should make gene therapy an increasingly important tool for the future of pediatric neurosurgery.