Cell Death Blocking Compound Developed

A compound that can keep cells alive and functioning in a perfectly healthy state when they otherwise would have died has been developed. The ability to swiftly intervene and prevent cell death, or apoptosis, could be game-changing for medical emergencies and procedures, such as minimizing cellular damage after heart attacks, or preserving organs for transplants.

The preclinical findings were published today in Nature Chemical Biology by a team of Australian scientists at Walter and Eliza Hall Institute of Medical and Monash University.

"Never before have we seen such promising ability to intervene in the earliest stages of apoptosis before irreversible damage occurs," Professor Guillaume Lessene, one of the authors, said.

Professor David Huang added that the ability to stop unwanted cell death could be invaluable for the future of medical care. "Acute injury can cause cells to die rapidly leading to the loss and weakening of tissues and muscles. In such circumstances, being able to prevent uncontrolled cell death could improve a patient's recovery, or even their chances of survival."

Apoptosis is controlled by the BCL-2 family of proteins. Within this family, some proteins promote cell survival, while others drive cell death. Proteins called BAK and BAX are involved in a critical step of cell death known as the point of no return. Cells are committed to die once either BAK or BAX is activated. According to the team, the compound successfully disabled BAK. "In laboratory models we found we could override apoptosis and keep cells functioning," Professor Benjamin Kile said. "We have shown it is possible to halt the biochemical cascade that triggers cell death, right at the point where it begins".

The proof-of-concept drug was developed through extensive medicinal chemistry following a high-throughput screening campaign of a quarter of a million potential small drug molecules.