Changing channels in pain and epilepsy: Exploiting ion channel gene therapy for disorders of neuronal hyperexcitability

Abstract

Chronic pain and epilepsy together affect hundreds of millions of people worldwide. While traditional pharmacotherapy provides essential relief to the majority of patients, a large proportion remains resistant, and surgical intervention is only possible for a select few. As both disorders are characterised by neuronal hyperexcitability, manipulating the expression of the most direct modulators of excitability - ion channels - represents an attractive common treatment strategy. A number of viral gene therapy approaches have been explored to achieve this. These range from the up- or down-regulation of channels that control excitability endogenously, to the delivery of exogenous channels that permit manipulation of excitability via optical or chemical means. In this review we highlight the key experimental successes of each approach and discuss the challenges facing their clinical translation.

Keywords: Chemogenetic; Chronic pain; Epilepsy; Gene therapy; Hyperexcitability; Ion channels; Optogenetic.