“Cell Death Blocker” Stops Healthy Cells From Dying

Institute scientists have developed a world-first compound that keeps cells alive and healthy when they otherwise would have died.

Before it’s too late

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, published in the journal Nature Chemical Biology, follow 11 years of collaborative research at the Walter and Eliza Hall Institute of Medical Research – a world leader in cell death studies. Professor Lessene, study co-author, said the new ‘cell death blocker’ was exceptional for its ability to keep cells alive and healthy in the laboratory.

“Never before have we seen such promising ability to intervene in the earliest stages of apoptosis before irreversible damage occurs,” Lessene said.

Invaluable for future of medicine

Professor Huang, fellow author, said 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, “said Huang.

Apoptosis is a form of tightly regulated cell death essential for health and development. This process 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.

Professor Kile, co-author, said the compound successfully disabled BAK. “In laboratory models we found we could override apoptosis and keep cells functioning,” he said. “We have shown it is possible to halt the biochemical cascade that triggers cell death, right at the point where it begins.”

Potential applications

The researchers are now looking to apply the knowledge to developing cell death blockers that are effective and safe in humans. Huang said the next steps would also involve applying the knowledge we have gained to more advanced models of disease.

“There could be applications for keeping cells alive to prevent degenerative diseases,” Huang said.

Reference

DeHoog, R. et al. (2019). Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies. PNAS. DOI: https://doi.org/10.1073/pnas.1911333116

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