AAV-Mediated Combination Gene Therapy for Neuropathic Pain: GAD65, GDNF, and IL-10
Dae-Wook Kim, Kyung-Ran Kim, Ye-jin Kwon, Minjung Kim, Min-Ju Kim, Yeomoon Sim, Hyelin Ji, Jang-Joon Park, Jong Ho Cho, Heonsik Choi, Sujeong Kim
Abstract
, with various combinations. The efficacy for pain relief was evaluated in a rat spared nerve injury model of neuropathic pain. The maximal analgesic effect was achieved when the AAVs expressing all three genes were administered to rats with neuropathic pain. The combination of two virus constructs expressing the three genes was named KLS-2031 and evaluated as a potential novel therapeutic for neuropathic pain. Single transforaminal epidural injections of KLS-2031 into the intervertebral foramen to target the appropriate dorsal root ganglion produced notable long-term analgesic effects in female and male rats. Furthermore, KLS-2031 mitigated the neuroinflammation, neuronal cell death, and dorsal root ganglion hyperexcitability induced by the spared nerve injury. These results suggest that KLS-2031 represents a promising therapeutic option for refractory neuropathic pain.