Antibody therapy developed by Scripps Research seems to offer over existing opioid-overdose treatments.
Scientists at Scripps Research have demonstrated that an antibody, in single-chain fragment variable (scFv) format, can bind to the powerful opioid carfentanil and reverse its overdose symptoms in preclinical tests.
Carfentanil is a derivative of the synthetic opioid fentanyl and is roughly 100 times stronger. It’s frequently combined with illicit substances like heroin and cocaine to intensify their euphoric sensations, leading to many fatal overdoses.
In the study, published in ACS Chemical Neuroscience on August 3, 2023, the researchers developed a human antibody that binds very tightly to carfentanil, fentanyl, and other fentanyl variants. In rodents, they showed that administering a solution of the antibody shortly after an overdose reverses the potentially deadly respiratory depression caused by carfentanil, the most dangerous of the variants. The results suggest that the antibody could be a more powerful, longer-lasting treatment for synthetic opioid overdose, compared to existing options.
“We expect this antibody to be a valuable new weapon for fighting the opioid crisis,” says study senior author Kim D. Janda, Ph.D., the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research.
The study’s first author was Lisa Eubanks, Ph.D., a senior staff scientist in the Janda laboratory.
Opioid drugs, whether synthetic or derived from the opium poppy, bind and activate neuronal receptors called mu-opioid receptors. These receptors are present on different types of neurons across the human nervous system, which is why opioid drugs have multiple effects like pain relief and euphoria, but also respiratory depression—slower and shallower breathing. Respiratory depression is the immediate cause of death in the tens of thousands of fatal opioid-related overdoses that occur each year in the U.S.
Carfentanil, after fentanyl, is the next-most common synthetic opioid found in illicit drugs in the U.S. Once available legally as a tranquilizer for large animals, it was pulled from the market by the FDA in 2018 because of its potential for misuse—and its potential lethality at doses measured in micrograms. Carfentanil is so potent that the U.S. government regards it as a possible chemical warfare agent; the Janda lab’s early work on the new antibody was funded in part by a National Institutes of Health program aimed at finding antidotes to such weapons.