Researchers at Scripps Research have created a vaccine that could potentially save lives by blocking the effects of xylazine, a sedative and pain reliever approved for use in animals that is now being added to illegal drugs like fentanyl, heroin, and cocaine. The combination of xylazine with these drugs has led to a sharp increase in overdose deaths, prompting the White House Office of National Drug Control Policy to declare it an emerging threat to the United States.
Xylazine, nicknamed the “zombie drug,” causes respiratory and central nervous system depression, and can heighten the effects of opioids. It also causes non-healing skin lesions and wounds that can require amputation in some cases. Currently, there is no specific treatment for xylazine poisoning other than supportive care, highlighting the need for effective measures to tackle its acute toxicity.
The Scripps Research team, led by senior author Kim D. Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry, has developed a vaccine that trains the immune system to attack xylazine. “We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says Janda. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”
The vaccine was created using a design principle pioneered by Janda, which involves pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant. The scientists tested three vaccine formulations to see which combination would create a robust immune response against xylazine.
In tests on rodents, one of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing. The vaccines also showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.
A provisional patent has been filed on the research, and Janda’s team plans to build on this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that the commonly used opioid overdose reversal drug naloxone cannot do.
“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”
The study, titled “Evaluation of a Hapten Conjugate Vaccine Against the ‘Zombie Drug’ Xylazine,” was co-authored by Mingliang Lin, Lisa M. Eubanks, Bin Zhou, and Kim D. Janda, all of Scripps Research. Funding for the study was provided by the Shadek family and Pearson Foundation.
This groundbreaking research offers hope in the fight against the growing threat of xylazine and its devastating effects when combined with other drugs. By developing a vaccine that can block the toxicity of xylazine, the Scripps Research team has taken a significant step towards finding an effective treatment for those affected by this dangerous substance.
As the opioid epidemic continues to claim lives across the United States, innovative solutions like this vaccine could play a crucial role in reducing overdose deaths and helping those struggling with substance use disorders. With further research and development, this vaccine may one day become a valuable tool in the fight against the “zombie drug” and its deadly consequences.