Opto-Opioids: Light-Activated Compounds for Locally-restricted and Reversible Pain Management

Background & Unmet Need

• Approximately 2.5 million people in the U.S. have Opioid Use Disorder, with over 80,000 opioid-related overdose deaths occurring in the US annually
• Opioid receptors are widely expressed across the nervous system, with central opioid receptors present in the CNS and peripheral opioid receptors present in the peripheral nervous system
• Given that many opioid-driven side effects, including respiratory depression and addiction, are centrally mediated in the brain, peripherally-restricted opioids provide a promising strategy for safer analgesia
• Light-activated ligands offer a promising approach for restricting the actions of opioids to the site of pain
• Unmet Need: New techniques that harness the analgesic power of opioids without the risk of addiction or respiratory depression

Technology Overview

• The Technology: Opioid analgesic compounds that can be locally and reversibly activated and deactivated with light, reducing addiction potential
• The Discovery: The inventors developed a morphine-based compound, azo-morphine-3 (AM-3), which has substantially stronger agonism for the mu-opioid receptor in the light-activated cis form than in the relaxed trans configuration
• PoC Data: Administration of cis-AM-3, but not trans-AM3, increased paw withdrawal latency (PWL) in the radiant-heat test with identical effect size to morphine (P>0.001 vs. vehicle)
• In vivo activation of AM-3 via paw illumination increased PWL in the same test (P>0.05), and demonstrated reversible and repeatable analgesic effects in the spared nerve injury model (SNI) of chronic neuropathic pain (P<.001)
• cis-AM-3 does not promote hyperlocomotion in the open field test, demonstrating lack of CNS activation

Technology Applications

• Topical and self-inactivating treatment for local control of acute pain
• Replacement for commonly prescribed opioids with less addiction potential

Technology Advantages

• Low penetration of the CNS, reducing potential for addiction and central side effects such as respiratory depression
• Avoids gut-based side effects seen with other peripheral opioids (e.g. loperamide)
• Pain relief is localized to pain site and is reversible
• Precursor compound, naltrexone, is not subject to controlled substance regulation