Optimization of a Gene Therapy for Chronic Pain in Human DRGs - 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.
