Neurology

Cell culture and mouse studies suggest antagonizing OPRL1 alone or in combination with inhibiting its downstream effector RTN4R could help treat SCI. In primary mouse cortical neurons subjected to scrape injury, an shRNA targeting OPRL1 increased regeneration of axons compared with a non-specific shRNA. In a mouse model of SCI, a tool compound OPRL1 antagonist increased the density of raphespinal nerve fibers in the spinal ventral horn and locomotion compared with vehicle. In another mouse model of SCI, the OPRL1 antagonist plus knockout of RTN4R increased the density of raphespinal nerve fibers in the spinal ventral horn, locomotion and motor coordination compared with the antagonist alone. Next steps could include identifying and testing RTN4R inhibitors in combination with OPRL1 antagonists in additional SCI models...