Project Summary/Abstract The goal of this project is design and optimize a gene therapy product that relieves pain in a non- permanent, non-addictive and long lasting manner. There are more than 100 million Americans suffering from chronic pain and current treatments consist mainly of opioid narcotics. However, opioids have severe side effects and are highly addictive. Voltage-gated sodium channels transmit pain signals in nociceptive neurons. Genetic studies have correlated a rare hereditary loss-of-function mutation in one channel isoform (NaV1.7) with a rare genetic disorder known as Congenital Insensitivity to Pain (CIP). Thus, selective repression of NaV1.7 could recapitulate the phenotype of CIP. However, the high homology of human NaV proteins, have frustrated most efforts to develop selective inhibitors. We have developed an innovative gene therapy approach to target NaV1.7 in vivo, and have demonstrated its efficacy in three murine models of pain. During this Phase I SBIR, we will optimize this gene therapy to target the human NaV1.7 sequence in human cell lines, and then we will choose the best designs to test them in human DRG neurons for potency, specificity, and efficacy in an ex vivo chemotherapy-induced neuropathic pain model. Thus, Navega’s final goal is to develop novel therapeutics that can mitigate pain through the use of specific gene therapy approaches to provide an alternative treatment to opioids for chronic pain.

Project Narrative According to the CDC, 8.0% of U.S. adults (19.6 million) suffer from high-impact chronic pain. Therapeutic options for these patients consist mainly of opioid narcotics, which come with side-effects and the risk of addiction. Based on our preclinical data in rodents, Navega Therapeutics’ proposal aims to optimize a gene therapy for chronic pain in human cell lines and human dorsal root ganglion neurons.