Targeted delivery of growth factors by HSV-mediated gene transfer for peripheral neuropathy

Dysfunction of peripheral nerves due to metabolic, toxic, infectious, or genetic causes is a common and debilitating syndrome resulting in sensory loss. Peripheral neuropathies are one of the most widespread neurological disorders, affecting nearly 20 million people in the United States alone. Pharmacologic treatment for peripheral neuropathies is one of the most challenging fields in the clinical research. Sensory neurons are widely distributed and relatively inaccessible to direct drug delivery. Targeted delivery of neurotrophic factors to the primary sensory afferent for treatment of polyneuropathy by gene transfer approach offers the possibility of a highly selective targeted release of bioactive molecules within the nervous system. Preclinical studies with non-replicating herpes simplex virus (HSV)-based vectors injected into the skin to transduce neurons in the dorsal root ganglion (DRG) have demonstrated efficacy in preventing progression of sensory neuropathy without any possible systemic side effects.