The molecule tested by Biotrial and produced by Bial exhibits numerous off-target effects, according to a study published in Science.
The suspicions on the BIA 10-2472 molecule are confirmed. A study published in the journal Science sheds new light on the “Biotrial affair”, a few months after the death of a man and the hospitalization of five other people following a clinical trial in January 2016.
The molecule tested in the Biotrial premises in Rennes and produced by the Bial laboratory has “off-target” effects, according to the team of researchers. It affects many enzymes in addition to the one the drug was supposed to inhibit.
Endocannainoid system
This is because BIA 10-2474 was supposed to inhibit only one enzyme, called Fatty Acid Amide Hydrolase (FAAH), which regulates the production of endocannabinoids. Previous work showed that inhibiting this enzyme in order to stimulate the endocannabinoid system (brain receptors involved in the sensation of hunger, pain, anxiety, etc.) did not induce severe toxic effects. The trail of an “off-target” effect, going beyond the targeted targets, has therefore emerged.
This lead is confirmed in this work carried out on human cells and based on complex techniques for analyzing the profile of proteins, making it possible to evaluate the activity of a molecule on a very large group of enzymes. The researchers compared the profile of BIA 10-2474 to that of another molecule that targets the FAAH enzyme exclusively.
High doses
However, the authors observed that at high doses, the Bial molecule disrupted the activity of lipases, enzymes involved in lipid cell metabolization. Some of the “off target” proteins were almost completely inhibited (over 90%).
These unexpected effects could explain the damage caused by taking the drug tested in the phase 1 clinical trial, although the causal relationship has not been proven. Side effects ranged from headaches to irreversible brain damage.
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