Modified form of botulinum toxin could replace opioids, notes new research
New research from UCL, the University of Sheffield and the Hospital for Sick Children, Toronto, has highlighted that a modified form of botulinum toxin gives long-lasting pain relief in mice without adverse effects, potentially leading to a replacement of opioid drugs.
In the study, which has been published in Science Translational Medicine, the researhcers deconstructed the botulinum molecule and reassembled it with an opioid called dermorphin to make Derm-BOT. This compound targets and silences pain signals from neurons in the spinal cords of mice.
“Injected into the spine, Derm-BOT relieves chronic pain — such as that caused by nerve damage — and avoids the adverse events of tolerance and addiction often associated with repeated opioid drug use,” explained co-corresponding author, Professor Steve Hunt (UCL Cell & Developmental Biology). “It doesn’t affect muscles like the botulinum toxin used to reduce wrinkles but it does block nerve pain for up to four months without affecting normal pain responses. It really could revolutionise how chronic pain is treated if we can translate it into clinic, removing the need for daily opioid intake.”
Opioids, which are the current standard of treatment for chronic pain have not been found to effectively treat the issue long-term as the body builds up a tolerance to repeated exposure. Additionally, they are know to cause negative side effects and potentially cause addiction by activation of the brain reward regions.
“We needed to find the best pain targeting molecular parts to direct the botulinum silencing ‘warhead’ to the pain-controlling system in the spine. For this, we developed a molecular Lego system which allows us to link the botulinum ‘warhead’ to a navigation molecule, in this case, the strong opioid called dermorphin, allowing the creation of widely desired long-lasting pain killers without the side effects of opioids,” added co-corresponding author Professor Bazbek Davletov from the Department of Biomedical Science at the University of Sheffield.
Over the course of five years, the researchers used 200 mice to simulate the early stages of human inflammatory and neuropathic pain. These mice were treated with a single injection of either Derm-BOT, SP-BOT (a substance P-modified botulinum molecule) or morphine and their behaviour was monitored to track pain-response as well as the locations and binding properties of the botulinum compounds.
“Both SP-BOT and Derm-BOT have a long-lasting effect in both inflammatory and neuropathic pain model, successfully silencing neurons without cell death. We were impressed to see that one tiny injection was enough to stop chronic pain caused by inflammation and nerve damage for at least a month,” concluded lead author, Dr Maria Maiarù (UCL Cell & Developmental Biology). “Furthermore, a single injection of Derm-BOT reduced mechanical hypersensitivity to the same extent as morphine. We hope to take our investigations forward with the aim of translating this into the clinic.”