Adolore BioTherapeutics 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.
- Findings highlight the advantages of Adolore’s approach for the delivery of proprietary gene therapy directly to specialized pain-sensing peripheral nerves (nociceptors) that mediate profound analgesia with the potential to address the great unmet need for non-opioid chronic pain therapies
- Data further supports the clinical-translational value of Adolore’s proprietary non-opioid analgesics for treating chronic non-cancer pain
- Company continuing progress with IND-enabling studies of ADLR-1001 gene therapy for the treatment of osteoarthritis (OA) chronic knee pain; Additional translational data expected before year-end
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.
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.”
Key Highlights
- CA8* gene therapy (rdHSV-CA8*, a research variant of ADLR-1001) prolongs nociceptor AHP resulting in decreased neuronal excitability, reducing nociceptive pain signaling.
- rdHSV-CA8*prolongs AHP via activation of Kv7 voltage-gated potassium channels.
- Administration of Kv7 specific inhibitor, XE-991 reverses the rdHSV-CA8*-induced prolongation of the AHP.
- These data further indicate that the selective upregulation of the Kv7 M-currents occurs in rdHSV-CA8* infected neurons only but not in controls.
- Results confirm that nociceptor treatment by rdHSV-CA8* specifically results in selective activation of Kv7 voltage-gated potassium channels reducing neuronal excitability and the subsequent propagation of pain signals.
Leveraging its innovative gene therapy vectors expressing CA8* analgesic peptides (ADLR-1001), Adolore is currently advancing two preclinical development programs: ADB-101 for the treatment of patients’ chronic pain caused by erythromelalgia, an orphan disease, and ADB-102, their lead program for the treatment of patients with chronic pain caused by knee OA. Based on substantial compelling preclinical data generated to date, the Company is progressing these programs toward IND filings and first-in-human clinical studies.
The Company’s lead development program for the treatment of chronic pain in knee osteoarthritis is fully funded by a UG3/UH3 grant awarded to the University of Miami by NIH/NINDS HEAL program to support all formal pre-clinical GLP/GMP/GCP development work through a first-in-human study of ADLR-1l01 in patients expected to commence in 2026.
About Carbonic Anhydrase-8 (CA8*) Gene Therapy
CA8* (variants of naturally occurring human carbonic anhydrase-8 analgesic peptides) gene therapies are a novel class of neuronal calcium channel inhibitors that activate Kv7 voltage-gated potassium channels and are administered locally and long-acting. Oral small molecule pain therapeutics that activate Kv7 voltage-gated potassium channels demonstrated proven analgesic efficacy before they were removed from the market due to severe adverse events related to systemic exposure and their metabolism. CA8* gene therapy provides versatile dosing regimens and routes of administration, including intra-articular, intra-neuronal (nerve block), and intradermal injection. This non-opioid CA8* mechanism-of-action addresses neuropathic, inflammatory, and nociceptive pain, which applies to a broad range of chronic pain indications. These conditions include osteoarthritis, lower back, and cancer pain; diabetes and other forms of peripheral neuropathy, including post-herpetic neuralgia; as well as rare pain conditions such as erythromelalgia, a heritable chronic pain condition, and orphan drug disease.
About Adolore BioTherapeutics, Inc.
Adolore BioTherapeutics, Inc., is a biotechnology company focused on developing novel therapies for treating chronic pain using a revolutionary intra-cellular replication-defective HSV (rdHSV) drug delivery platform that is disease-free, non-toxic, and permits localized peripheral nervous system delivery of proprietary biotherapeutics. This rdHSV gene therapy technology incorporates an established re-dosing strategy and an excellent safety profile. HSV vectors are known for their stability and prolonged gene expression, providing an excellent basis for the long-term treatment of chronic pain conditions. Our best-in-class CA8* programs are long-acting, locally acting gene therapies that are opioid-free Disease-Modifying Anti-Pain therapies (DMAPs) designed to treat many forms of chronic pain.
The Company’s current CA8* gene therapy programs are in preclinical development for the treatment of patients suffering from erythromelalgia, a lifelong heritable chronic pain condition representing an orphan drug disease with no approved therapy, and chronic pain due to knee osteoarthritis, affecting a large number of patients that are often treated with opioids due to the lack of good alternatives, thus contributing to the ongoing opioid crisis.
For more information, visit adolore.com.
Forward-Looking Statements
To the extent, this announcement contains information and statements that are not historical, they are considered forward-looking statements within the meaning of the federal securities laws. You can identify forward-looking statements by the use of the words “believe,” “expect,” “anticipate,” “intend,” “estimate,” “project,” “will,” “should,” “may,” “plan,” “intend,” “assume” and other expressions which predict or indicate future events and trends and which do not relate to historical matters. You should not rely on forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, some of which are beyond the control of the Company. These risks and uncertainties include but are not limited to, those associated with drug development. These risks, uncertainties, and other factors may cause the actual results, performance, or achievements of the Company to be materially different from the anticipated future results, performance, or achievements expressed or implied by the forward-looking statements.
Investor Relations Contact:
JTC Team, LLC
Jenene Thomas
833-475-8247
adolore@jtcir.com
SOURCE: Adolore Biotherapeutics, Inc.
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