A drug originally approved to treat alcohol addiction may help prevent cell death and inflammation caused by severe trauma—especially in females—according to new research published in Science Translational Medicine on May 28.
The study, led by surgeon-scientists, found that disulfiram, a medication used for alcohol use disorder, could interrupt the harmful cascade of cell death and immune response that follows traumatic injuries like car crashes or major falls. This discovery could pave the way for new treatments that, if administered within hours of injury, might reduce tissue damage, improve survival rates, and shorten hospital stays.
“We have many treatments for diseases like cancer and autoimmune disorders, but almost none for trauma, which is a leading cause of death in young people,” said senior author Dr. Timothy Billiar. “Our work is moving toward a personalized, biomarker-driven approach to trauma care.”
Previous research showed that trauma causes a rapid release of cellular contents, followed by widespread inflammation—even in uninjured organs. While this immune response can be helpful in minor injuries, in severe trauma it often leads to complications like organ failure.
To better understand this, the researchers studied mice—importantly including both males and females, which is rare in such studies. They tested four drugs that each block a different type of cell death. All showed some benefit, but the most effective was disulfiram, which blocks a molecule called gasdermin D. This molecule triggers a form of cell death known as pyroptosis, which causes cells to burst and release inflammatory signals.
Mice genetically engineered to lack gasdermin D also showed reduced trauma responses, reinforcing the idea that targeting this pathway could be key. Notably, female mice responded even more strongly to the treatment than males.
“This sex-based difference is striking,” said Billiar. “It suggests that trauma treatments could be tailored—perhaps using gasdermin D inhibitors for women and different strategies for men.”
The next steps include testing in larger animals and eventually in humans, along with developing more targeted drugs to minimize side effects.