Adolore BioTherapeutics Announces Publication Demonstrating Carbonic Anhydrase-8 Gene Therapy (rdHSV-CA8) Decreased Pain-Sensing Neuronal Excitability by Activating Kv7 Voltage-Gated Potassium Channels

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DELRAY BEACH, FL / ACCESSWIRE / May 16, 2024 / Adolore BioTherapeutics ("Adolore" or the "Company"), a biotechnology company focused on developing breakthrough opioid-free gene therapy treatments for chronic pain, today announced the publication of its manuscript titled, " rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels,[1]" in the peer-reviewed journal, Frontiers in Molecular Neuroscience.

Foto: Accesswire

Roy Clifford Levitt, MD, Clinical Professor at the University of Miami, Principal Investigator and Program Director of the NIH, NINDS, HEAL Award supporting ADLR-1001 development for the treatment of chronic knee pain due to OA, and Founder & Executive Chairman of Adolore BioTherapeutics, highlighted data from preclinical electrophysiological studies of their gene therapy expressing a human carbonic anhydrase-8 variant peptides (CA8*). This manuscript demonstrates that when CA8* expression is increased in nociceptors (specialized pain-sensing neurons), it can attenuate their excitability via a mechanism that involves CA8-induced prolongation of their afterhyperpolarization (AHP) resulting from the activation of cell membrane Kv7 voltage-gated potassium channels. The specificity of the treatment was confirmed using a null-mutant CA8* gene therapy vector and in vitro drug-mediated (XE-991) selective antagonism of the Kv7 channels.

Dr. Levitt, commented, "Kv7 channels remain important analgesic targets. Kv7 voltage-gated potassium channel activators that open these channels and hyperpolarize nociceptors are well-known to produce potent non-opioid-based analgesia in many human chronic pain conditions. Kv7 openers have been successfully translated from animal models to human chronic pain conditions. Based on our findings, we believe that the activation of Kv7 channels by CA8 gene therapy mediated by the reduction of cytoplasmic free calcium explains the analgesia observed through prolonged afterhyperpolarization (AHP) and reduced neuronal excitability. Bolstered by our substantial body of data, we continue to develop our innovative approach to address the significant serious unmet need for safe and effective locally acting pain therapies to replace opioids. Our preclinical data strongly support continued preclinical development toward an IND and clinical studies of ADLR-1001."