A Human Antibody Proven Effective in Treating Opioid Overdose
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A Human Antibody Proven Effective in Treating Opioid Overdose
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A Human Antibody Proven Effective in Treating Opioid Overdose.
Researchers have developed a human antibody targeting opioid drugs like fentanyl and its derivatives.
This antibody has demonstrated a superior ability to block the effects of these drugs and reverse overdose compared to existing therapies.
The novel antibody treatment is currently undergoing clinical trials and could offer a more effective approach to managing life-threatening opioid overdoses.
In 2021, the total number of deaths due to opioid overdose in the United States exceeded 80,000, with synthetic opioids accounting for a significant portion.
Opioid drugs, whether natural or synthetic, selectively bind to the μ-opioid receptors in the brain, leading to pain relief, sedation, euphoria, and respiratory depression—the latter being a major contributor to overdose and death. Fentanyl and its structurally related variants are among the primary culprits.
Fentanyl is approximately 100 times more potent than morphine and up to 50 times more potent than heroin.
Carfentanil, a derivative, is considered one of the most potent opioid drugs commercially available, being about 10,000 times stronger than morphine.
Given that carfentanil was designed as an elephant tranquilizer, this extreme potency is not surprising
. Despite the removal of carfentanil from the market by the U.S. Food and Drug Administration (FDA), it has found its way to the streets, often mixed with heroin and cocaine.
Researchers at the Scripps Research Institute in California have developed a human antibody that can bind to carfentanil and other fentanyl variants, offering a more effective reversal of potentially fatal overdose effects than current treatment methods.
Lead author of the study, Kim Janda, stated, “We hope this antibody becomes a valuable new weapon to combat the opioid crisis.”
Treating carfentanil overdose poses a challenge due to its potency and strong binding to the μ-opioid receptors.
The primary treatment method currently used is naloxone, which binds to opioid receptors and blocks the drug’s effects.
However, naloxone’s short duration of action may render it ineffective against carfentanil overdose.
Thus, researchers embarked on developing a human antibody specific to fentanyl as a potential solution.
They administered a designed molecule to rats to induce the production of antibodies against fentanyl and its derivatives.
These rats were genetically engineered to produce human antibodies, avoiding the need for direct human injections and potential immune reactions.
Several antibodies with strong binding affinity to carfentanil were identified and the most effective one was selected.
This antibody was further engineered to be more lightweight, allowing quicker entry into the bloodstream, and to have an extended active life within the bloodstream.
The antibody, produced in the form of a single-chain variable fragment (scFv), is a small-sized synthetic construct that retains the antigen-binding properties of the corresponding immunoglobulin G (IgG) antibody, the most common antibody type.
Testing the optimized scFv antibody named C10-S66K on rats showed its ability to significantly reduce the impact of carfentanil on the brain.
After injection, it could reverse respiratory depression within 15 minutes of exposure to a large amount of carfentanil.
About 40 minutes later, its effects were stronger than naloxone and continued to strengthen after two hours, whereas naloxone’s effects peaked at 30 minutes and quickly diminished.
X-ray crystallography was used to study the structure of C10-S66K in complex with carfentanil and fentanyl, showing the antibody’s effective binding to various fentanyl derivatives without interfering with naloxone treatment.
Clinical trials for the C10-S66K antibody are set to begin later this month.
Meanwhile, the FDA has approved the full-length IgG version of the antibody, CSX-1004, for clinical trials aimed at preventing fentanyl overdose, with trials scheduled to start this month.
The study was published in the journal “ACS Chemical Neuroscience.”
A Human Antibody Proven Effective in Treating Opioid Overdose
(source:internet, reference only)
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