Exploiting the neurotherapeutic potential of peptides: targeted delivery using HSV vectors

Abstract

Neurotrophic factors and peptide neurotransmitters represent two classes of potent macromolecules whose therapeutic use in the treatment of neurologic disease is limited by unwanted effects that result from the widespread distribution of cognate receptors within and beyond the neuraxis. Targeted gene delivery to sensory neurons of the dorsal root ganglion (DRG) by subcutaneous inoculation of herpes simplex virus (HSV)-based gene transfer vectors may be used to achieve local expression and release of these pleiotropic, short-lived molecules in a restricted area. Recent studies demonstrate that HSV-mediated transfer of genes coding for neurotrophic factors prevents the progression of disease in animal models of drug-induced or diabetic polyneuropathy and that HSV-mediated transfer of genes coding for inhibitory neurotransmitters provides a regional analgesic effect in animal models of chronic pain. The first human trial of HSV-mediated gene transfer to DRG is about to commence. HSV-mediated gene transfer may allow the therapeutic potential of these peptides for the treatment of neurologic disease to be realised.