Gene therapy for the treatment of chronic peripheral nervous system pain

Chronic pain is a major health concern affecting 80 million Americans at some time in their lives with significant associated morbidity and effects on individual quality of life. Chronic pain can result from a variety of inflammatory and nerve damaging events that include cancer, infectious diseases, autoimmune-related syndromes and surgery. Current pharmacotherapies have not provided an effective long-term solution as they are limited by drug tolerance and potential abuse. These concerns have led to the development and testing of gene therapy approaches to treat chronic pain. The potential efficacy of gene therapy for pain has been reported in numerous pre-clinical studies that demonstrate pain control at the level of the spinal cord. This promise has been recently supported by a Phase-I human trial in which a replication-defective herpes simplex virus (HSV) vector was used to deliver the human pre-proenkephalin (hPPE) gene, encoding the natural opioid peptides met- and leu-enkephalin (ENK), to cancer patients with intractable pain resulting from bone metastases (Fink et al., 2011). The study showed that the therapy was well tolerated and that patients receiving the higher doses of therapeutic vector experienced a substantial reduction in their overall pain scores for up to a month post vector injection. These exciting early clinical results await further patient testing to demonstrate treatment efficacy and will likely pave the way for other gene therapies to treat chronic pain.

► Gene therapy represents a novel treatment for chronic peripheral nervous system pain.
► Each viral vector system has features that make them amenable to certain therapies.
► Cell-based therapies have not been as efficacious as viral-based therapies.
► Safety, immunity, toxicity and long-term expression remain key issues to solve.
► The NP2 pain Phase-I clinical trial demonstrated safety and efficacy.