Human Cells Predict Danger of Lethal Drug That Animal Tests Missed
Study in a Sentence: An international group of scientists collaborated to study why experimental drug compound BIA 10-2474 killed one previously healthy clinical trial volunteer and caused brain damage in four others, when other FAAH inhibitors have been shown to be safe, by using activity-based protein profiling (ABPP) to screen the compound using human cells and brain tissues.
Healthy for Humans: They found that BIA 10-2474 disrupted the activity of several lipases, including an off-target enzyme that has been linked to rare neurological disorders, suggesting BIA 10-2474 may disrupt how neurons in the brain metabolize lipids.
Redefining Research: The off-target effects found using ABPP were not seen in experiments on mice, rats, monkeys, and dogs. This human-based model can be used to study on-target engagement and off-target activity in humans without sacrificing animal lives.
This image shows a model of FAAH inhibitor BIA 10-2474. Image Credit: Medical Facts
Van Esbroeck ACM, Janssen APA, Cognetta AB 3rd. Activity-based protein profiling reveals off-target protein of the FAAH inhibitor BIA 10-2474. Science. 2017;356:1084-1087. DOI: 10.1126/science.aaf7497
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