Experimental mRNA therapy dramatically extends treatment window for acetaminophen overdose in preclinical models
When a patient arrives at the hospital with an acetaminophen overdose, it's often a race against the clock. The only FDA-approved antidote for overdose-related liver injury, N‑acetylcysteine, must be administered within hours to be effective.
Acetaminophen overdose, a common cause of emergency room visits for liver failure, can be treated with N-acetylcysteine within a few hours of ingestion. However, a new study from researchers at the University of Pittsburgh has identified a liver-protection pathway that could extend this treatment window. The experimental mRNA therapy, delivered via lipid nanoparticles, reduced liver injury in mice even six hours after an overdose.
The therapy works by activating a protein called SRXN1, which helps reverse oxidative damage and protect another protein, USP7, that stabilizes an antioxidant-defense molecule called HO-1. In the study, mice without SRXN1 experienced significantly more severe liver injury after an overdose, while mice with elevated SRN1 levels were protected.
The researchers believe this discovery could lead to a new treatment for acetaminophen overdose, although further research is needed to determine if the approach is effective in humans.
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