A crystal structure of the optimized antibody, C10-S66K. Credit: Scripps Research
Scientists at Scripps Research have published their findings regarding an antibody that tightly binds to the synthetic opioid Carfentanil, reversing the effects of an overdose. In testing, researchers found that by administering a solution of the antibody shortly after the onset of an overdose, the respiratory depression caused by Carfentanil was reversed.
Carfentanil, a variant of the synthetic opioid fentanyl, is around 100 times more potent and is the second most common synthetic opioid found in illicit drugs within the United States. The drug works by binding to mu-opioid receptors that are found throughout the nervous system. This wide spread of binding is what allows the drug to have numerous effects including euphoria and pain relief, however, it can also lead to respiratory depression, the leading cause of death in fatal opioid overdoses each year.
In the study, published in ACS Chemical Neuroscience, researchers discovered that the optimized C10‐S66K antibody in single-chain fragment variable (scFv) format, had much stronger effects than current treatment options. Current treatments, including naloxone and naltrexone, are often ineffective against synthetic opioids even when used in high quantities.
When injected after a large exposure to carfentanil, C10‐S66K had a powerful effect on reducing respiratory depression. forty minutes after injection, the antibody had a stronger effect than naloxone and was still increasing for nearly two hours, whereas naloxone’s effects peak at thirty minutes and drop off sharply after.
“We expect this antibody to be a valuable new weapon for fighting the opioid crisis,” says study senior author Kim D. Janda, PhD. The researchers have licensed the rights for further development and marketing to Cessation Therapeutics and clinical trials are anticipated to begin this month.