Scientists at Scripps Research have made a promising breakthrough in the treatment of carfentanil overdose. Carfentanil is a highly potent synthetic opioid that is commonly mixed with illegal drugs like heroin and cocaine, leading to fatal overdoses. In preclinical tests, researchers developed an antibody in single-chain fragment variable (scFv) format that binds to carfentanil and other fentanyl variants, reversing signs of overdose in rodents.
Published in ACS Chemical Neuroscience, the study showcased the potential of the antibody to be a more powerful and longer-lasting treatment for synthetic opioid overdose compared to existing options. The researchers vaccinated rodents with a molecule that would trigger the production of human antibodies against carfentanil and fentanyl variants. They then identified several antibodies that bound to carfentanil with high affinity and selected the most potent one, modifying it to be lightweight and persistent in the bloodstream.
Tests on rodents demonstrated that the optimized scFv antibody, named C10-S66K, was successful in reducing carfentanil’s effects on the brain. The antibody was administered via a simple intramuscular injection, causing a reversal of carfentanil-driven respiratory depression. The effects were stronger and longer-lasting compared to existing treatments like naloxone.
The structural data, determined by the collaborating laboratory of Ian Wilson, indicated that the antibody should bind effectively to multiple fentanyl derivatives without interfering with other beneficial opioid molecules. With these promising results, Scripps Research has licensed the rights to further develop and market the antibody to pharmaceutical company Cessation Therapeutics. Clinical trials for the prevention of fentanyl overdose using a full-length IgG version of the antibody, termed CSX-1004, have received approval from the U.S. Food and Drug Administration (FDA) and are scheduled to begin this month.
This antibody could be a valuable new weapon in the fight against the opioid crisis, said study senior author Kim D. Janda, the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research. The development of a more effective and long-lasting treatment for synthetic opioid overdose has the potential to save countless lives and address a critical issue plaguing communities worldwide.
