Herpes vector-mediated gene transfer in treatment of diseases of the nervous system

Abstract

Vectors constructed from recombinant herpes simplex virus (HSV) have special utility for gene transfer to the nervous system. Nonreplicating vectors created by deletion of essential immediate early genes can be propagated to high titers on complementing cell lines that provide the missing gene product(s) in trans. Direct inoculation of these vectors into neural parenchyma is effective in rodent models of brain tumor, Parkinson disease, spinal cord injury, and spinal root trauma. Subcutaneous inoculation of the HSV vectors can be used to transduce neurons of the dorsal root ganglion to provide a therapeutic effect in models of polyneuropathy and chronic regional pain. In human trials, direct injection of replication-competent HSV into brain tumors has proven safe. Human trials of nonreplicating HSV gene transfer by direct inoculation for treatment of glioblastoma and HSV gene transfer by subcutaneous inoculation for the treatment of chronic intractable pain should commence soon.