Repurposing a Drug to Thwart Cell Death

Apoptosis (also known as programmed cell death) is a normal biological process. But uncontrolled apoptosis all too often accompanies heart attacks and strokes as well as neurodegenerative diseases. A protein called BAX has been dubbed the cellular “executioner” because of its central role in triggering apoptosis.

Evripidis Gavathiotis, Ph.D., and colleagues have discovered that the drug eltrombopag (previously already approved by the Food and Drug Administration for increasing blood platelet counts in people with chronic immune thrombocytopenia) potently inhibits BAX and the apoptosis it causes. This finding suggests that eltrombopag should be evaluated for its ability to inhibit BAX-mediated apoptosis in heart attacks and other pathological conditions.  The study was published online on February 18 in Nature Communications.

The researchers identified eltrombopag’s BAX-inhibiting ability by chance due to its structural similarity to a compound that Dr. Gavathiotis had earlier found binds to BAX. He and his team also identified the molecular mechanism by which eltrombopag interacts with BAX to inhibit apoptosis—information that could serve as a blueprint for developing future BAX inhibitors.

Dr. Gavathiotis is professor of biochemistry and of medicine at Einstein.