Virus-Delivered Gene Therapy Provides Hope for Neuropathic Pain Relief

PainRelief.com: What are the main findings?

Response: A single transforaminal epidural injections of KLS-2031 to target the appropriate dorsal root ganglion (DRG) produced notable long-term analgesic effects in both female and male rats. The three therapeutic genes expressed from KLS-2031 synergistically inhibit the major pathological mechanism of NP. The superior analgesic effect of KLS-2031 is the result of a multiple-target approach, which suppressed neuronal hyperactivity, damage, and neuroinflammation. The therapeutic genes delivered by KLS-2031 not only reverse these neuropathological changes but also normalize the excitability of peripheral nerves, indicating that this treatment controls pain sensation while promoting a favorable environment for nerve function.

PainRelief.com: What should readers take away from your report?

Response: KLS-2031 has shown long-term analgesic effect. It reduced the number of apoptotic cells and activated microglia in the DRG, and restored the sensitivity and excitability of small-sized neurons in the DRG, which are known to contain pain-signaling c-fibers. Our study demonstrated that KLS-2031 not only alleviates NP symptoms but also achieves neurophysiological improvement. These findings demonstrate the potential success of NP treatment by targeting multiple aspects of complex underlying pathophysiology.

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: So far, we have studied the mechanism of action (MOA) of KLS-2031 in the peripheral nervous system, and we will continue to study the MOA of KLS-2031 in the central nervous system. Furthermore, based on the finding that DRG neuronal excitability was significantly increased in the neuropathic pain model and recovered by KLS-2031 treatment, we are planning to examine the precise mechanism by which neuronal excitability is modulated by KLS-2031.

PainRelief.com: Is there anything else you would like to add?

Response: KLS-2031 has the potential to address unmet medical needs for neuropathic pain. We have demonstrated that a single administration of KLS-2031 has long-term efficacy and has the potential to be a disease-modifying agent. KLS-2031 is currently undergoing a phase1/2a clinical trial for the treatment of lumbosacral radiculopathy in the USA.

Citation:

Kim, Daewook & Kim, Kyung-Ran & Kwon, Yejin & Kim, Minjung & Kim, Min-Ju & Sim, Yeomoon & Ji, Hyelin & Park, Jang-Joon & Cho, Jong-Ho & Choi, Heonsik & Kim, Sujeong. (2020). AAV-mediated combination gene therapy for neuropathic pain: GAD65, GDNF, and IL-10. Molecular Therapy – Methods & Clinical Development. 18. 10.1016/j.omtm.2020.06.018.

https://www.sciencedirect.com/science/article/pii/S232905012030142X

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