Scientists at Scripps Research have created an antibody capable of counteracting the dangerous effects of the potent opioid carfentanil, as shown in preclinical tests. Named C10-S66K, this new antibody therapy could present a more robust and enduring solution for synthetic opioid overdoses compared to existing treatments.
The research on the antibody highlights its ability to bond with carfentanil, a fentanyl derivative that is around 100 times more potent. Carfentanil is often mixed with illegal drugs such as heroin and cocaine to heighten their euphoric effects, resulting in numerous fatal overdoses.
The study, published in ACS Chemical Neuroscience on August 3, 2023, reveals the development of a human antibody that binds tightly to carfentanil, fentanyl, and other similar variants. Tests on rodents demonstrated that administering the antibody shortly after an overdose could reverse the potentially fatal respiratory depression brought on by carfentanil, among the most hazardous of the variants. The findings point to a more effective and longer-lasting alternative for treating synthetic opioid overdoses than current methods.
The researchers, led by study senior author Kim D. Janda, Ph.D., and first author Lisa Eubanks, Ph.D., envision the antibody as an essential new tool in combating the opioid crisis.
Opioid drugs affect the human nervous system by binding to neuronal receptors called mu-opioid receptors. This binding produces effects such as pain relief and euphoria but can also cause respiratory depression, a potentially deadly side effect. Respiratory depression is the immediate cause of death in the numerous opioid-related overdoses that occur in the U.S. each year.
Carfentanil, considered a possible chemical warfare agent by the U.S. government, was once used as a tranquilizer for large animals but was removed from the market due to its potential for misuse and lethal effects.
Currently, fentanyl and carfentanil overdoses are treated with drugs like naloxone and naltrexone. These treatments sometimes fall short against synthetic opioids and offer benefits that last less than an hour, allowing potentially lethal effects to recur.
To develop a more effective antidote, Janda’s team aimed to create an antibody that would bind strongly to fentanyl and its derivatives, stay in the body for an extended period, and be easily administered. They vaccinated rodents with a specially designed molecule to produce human antibodies against carfentanil, fentanyl, and their variants. The most potent of these antibodies was selected and modified for quick entry into the bloodstream and prolonged persistence.
Rodent tests showed that the optimized scFv, C10‐S66K, effectively reversed the carfentanil-induced respiratory depression. Its effect lasted longer than existing treatments, peaking at 40 minutes and continuing to increase after two hours, while current treatments like naloxone peak at 30 minutes and quickly decrease.
Collaborating with Ian Wilson, Ph.D., the team used X-ray crystallography to determine the structures of carfentanil- and fentanyl-bound C10‐S66K. The structural data indicate that the antibody should bind well to various fentanyl derivatives without interfering with other beneficial opioid molecules.
The rights to further develop and market C10-S66K have been licensed to Cessation Therapeutics, with the FDA approving a full-length IgG version termed CSX-1004 for clinical trials scheduled to commence this month for the prevention of fentanyl overdose. The study was funded by the National Institute on Drug Abuse.
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Frequently Asked Questions (FAQs) about fokus keyword carfentanil
What is the new development in treating potent opioid carfentanil overdoses?
Scientists at Scripps Research have developed an antibody, known as C10-S66K, that can effectively reverse the life-threatening effects of carfentanil, a synthetic opioid that is 100 times stronger than fentanyl. This new antibody therapy may provide a more robust and enduring solution for synthetic opioid overdoses than existing methods.
How does the newly developed antibody work against carfentanil?
The antibody binds tightly to carfentanil, fentanyl, and other similar variants. It was shown in rodent tests to reverse potentially fatal respiratory depression caused by carfentanil. The optimized scFv, C10‐S66K, has been demonstrated to have a powerful and lasting effect, offering a more effective and longer-lasting treatment for synthetic opioid overdose.
What makes carfentanil a particularly dangerous opioid?
Carfentanil is roughly 100 times more potent than fentanyl and is frequently mixed with illicit drugs such as heroin and cocaine to amplify their effects. This often leads to fatal overdoses. The U.S. government even regards carfentanil as a possible chemical warfare agent, highlighting its extreme potency.
How does this new antibody compare to existing treatments for synthetic opioid overdoses?
The new antibody offers a more potent and longer-lasting treatment compared to existing options like naloxone and naltrexone. In rodent tests, C10‐S66K showed a stronger effect even 40 minutes after injection, while traditional treatments peaked at 30 minutes and quickly declined.
Are there plans to commercialize the newly developed antibody for treating opioid overdoses?
Yes, Janda and Scripps Research have licensed the rights to further develop and market C10-S66K to Cessation Therapeutics. The FDA has approved a full-length IgG version of this antibody, CSX-1004, for clinical trials set to begin soon for the prevention of fentanyl overdose.
More about fokus keyword carfentanil
- Scripps Research
- ACS Chemical Neuroscience
- National Institute on Drug Abuse
- U.S. Food and Drug Administration (FDA)
- Cessation Therapeutics (Note: The link to Cessation Therapeutics is not provided in the original text, so it may need to be found or omitted.)
