Gene therapy for the central nervous system in the lysosomal storage disorders.

ABSTRACT

Although great promise has been made in the field of gene therapy, a number of difficulties must be solved before successful human studies can be completed. These issues involve safety, immunological reactions to the vectors and their transgene products, persistent transgene expression, and ability to repeat administrations of the vector safely. A major hurdle that must be overcome is the ubiquitous delivery of the transgene throughout the nervous system. Significant gene delivery to the CNS of murine models of LSD has been accomplished, but we await the successful treatment of the nervous system in a larger mammalian model of LSD. As yet there is no perfect vector that can solve all of these problems. It is likely that vector technology will evolve into hybrid vectors also using synthetic components that will increase safety and efficacy of recombinant vectors. The treatment of the CNS remains complicated, but progress is being made in this area. Clinical trials already planned will give us increasing information as to the ideal gene therapy for the CNS.