Experimental vaccine blocks fentanyl and related drugs before reaching the brain in animal studies.
Scientists at Scripps Research have developed an experimental vaccine that may protect against fentanyl overdoses by stopping the dangerous effects of the drug from reaching the brain. Early studies in mice suggest the vaccine could defend against fentanyl itself as well as several of its dangerous chemical relatives, helping in the fight against the nation’s opioid crisis.
Fentanyl has become one of the deadliest drugs in the United States. The synthetic opioid is many times more potent than heroin and morphine, and even tiny amounts can slow or stop breathing. Many overdose deaths occur because fentanyl is mixed into other illegal drugs without the user’s knowledge or because powerful new versions of the painkiller appear faster than health officials can respond. Current treatments, including naloxone (branded Narcan), can reverse an overdose, but they must be given to a person very quickly. Researchers have been searching for alternative ways to prevent overdoses, even before they happen rather than treating them after the fact.
Instead of acting on the brain, the new vaccine trains the immune system to recognize fentanyl-like drugs circulating in the bloodstream. Antibodies produced by the body attach to the drug molecules and keep them from crossing into the brain, where they cause their most dangerous effects. What makes this vaccine different from earlier attempts is that it does not focus only on fentanyl itself. Researchers designed it to recognize a wider family of related drugs, including modified versions that illegal manufacturers frequently create to increase potency or avoid regulation.
Kim Janda, a chemistry professor at Scripps Research and senior author of the study, said the findings suggest scientists may no longer have to chase each new synthetic opioid individually, but rather, can address the underlying issues of each simultaneously. The research team built the vaccine using a specially designed molecule that shares some features with fentanyl but has a different core structure. Conventional thinking has held that vaccines against drugs should closely resemble the drug they are trying to block. This new design challenged that long-held belief by presenting the immune system with a molecule that looked significantly different while still sharing its critical characteristics.
To test the vaccine, researchers attached the modified molecule to a carrier protein and gave mice four doses over an eight-week period, and they were pleasantly surprised by the results. The animals produced antibodies that recognized fentanyl and several related compounds, including carfentanil, acetylfentanyl, furanylfentanyl and China White. These substances are among the most dangerous illicit synthetic opioids, responsible for many overdose fatalities each year. At the same time, the antibodies did not attach to commonly prescribed opioids such as morphine or oxycodone. That distinction could be important if the vaccine eventually reaches human trials because it may allow patients to continue receiving safer pain medications when medically necessary.
Researchers then tested how well the vaccine protected the mice against devastating effects of these drugs. The vaccine helped the rodents maintain nearly normal breathing even after being exposed to fentanyl doses that would normally cause severe respiratory problems. The team also found that fentanyl levels in the brains of vaccinated mice were about 70 percent lower than in unvaccinated animals. The finding suggests the antibodies successfully trapped much of the drug in the bloodstream before it could affect the brain.
While the research team stressed that the new vaccine is still years away from becoming available to the general population, they also stated it offers hope for an eventual, preventive option for those recovering from opioid addiction or who are considered at high risk of accidental fentanyl exposure.
Sources:
New fentanyl vaccine blocks deadly overdoses before they start
Join the conversation!