A new drug molecule that can block cell death could hold the potential for a range of regenerative treatments.

Apoptosis is a form of controlled cell death that is essential for normal development and body function. The BLC-2 family of proteins control the process, with some protein molecules promoting cell survival and others promoting cell death. Coaxing cells to undergo controlled death is a viable treatment for cancer, as it prevents the excessive proliferation that can lead to tumours. However, being able to prevent cell death also holds therapeutic benefit, to enable easier recovery after acute injuries.

Previous research has focused on stopping apoptosis in its later stages, despite little success. In this study, researchers aimed to intervene in apoptosis at a much earlier stage that is controlled by the proteins BAK and BAX. Once BAK and BAX are activated the cell has reached a ‘point of no return’ and is guaranteed to die. Apoptosis cannot take place if these proteins remain inactivated.

The team screened 250,000 small molecules for their potential to block the two proteins. The compound WEHI-9625, a tricyclic sulfone, was able to prevent cells that were ‘sentenced to death’ from undergoing apoptosis. The cells were able to retain their normal function.

Further investigation in mice models showed that WEHI-9625 acted to block mice BAK. CRISPR studies demonstrated that another cell protein, VDAC2, was required to ensure WEHI-9625 could block the function of BAK. It was determined that WEHI-9625 works by promoting the interaction of VDAC2 and BAK. During apoptosis, VDAC2 and BAK were shown to dissociate suggesting that the stabilising interaction between the two proteins can prevent cell apoptosis.

Acute injury can often lead to many cells dying rapidly. Being able to put a stopper on cell death could increase patient’s survival chances and aid their recovery significantly.