Keeping Neurons Alive

A Breakthrough in Switching Off Cell Death.

In every moment of every day our bodies are undergoing a constant cycle of death and renewal. Not that we notice it, because it all happens at the cellular level in a process called apoptosis, from the Greek for “falling off,” as in leaves falling off a tree.

Millions of cells die and are replaced by new ones. At least that is how it’s supposed to work in healthy bodies. It’s only when things go awry that we feel the effects.

When brain cells die prematurely, it can lead to neurodegenerative conditions like Parkinson’s or Alzheimer’s.

Now, researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, have discovered a means of stopping these crucial cells from dying, a finding with a tantalizing potential for the treatment of diseases that currently have no cure. It is detailed in a research paper published in Science Advances in March 2025.

 “Our focus currently is Parkinson’s, but it could be very applicable to other neurodegenerative diseases such as Alzheimer’s,” said Dr. Grant Dewson, co-corresponding author of the study and head of the WEHI Parkinson’s Disease Research Centre.

Right now, there are no disease-modifying therapies for Parkinson’s, so in terms of being able to stop that disease progression, that’s where I think we can hopefully in the future have a major impact.

He was speaking to Mind Over Matter® from his office in Melbourne, joined by co-corresponding author Dr. Guillaume Lessene, who added: “We’re not claiming that what’s in the paper is a drug to be given to humans. It’s what we call a proof of concept compound that helps us validate our hypothesis.”

Their project built upon a landmark discovery made at the same research institute almost 40 years ago, a revelation that brought a new way of looking at cancer cells. 

Previously, it was believed that cancer was only the result of too many cells growing uncontrollably. The Australian researchers found that actually cancer cells are prevented from dying when they should.

Decades later, the discovery led to the development of a series of new anti-cancer drugs that are in clinical trials, with one approved for people with leukemia.

Doctors Dewson and Lessene and their team approached the phenomenon from a different angle: What if they could find a way to keep cells, particularly brain cells, from dying prematurely? They hypothesized that there might be a molecular compound that could disable a protein called BAX that causes cell death.

In the search for that particular molecule, the cliché “needle in a haystack” perfectly applied, as the team examined a massive number of potential candidates.

“It’s a very complex process, with hundreds of thousands of different chemicals. We wanted to see which ones either interact with that particular protein, or if they actually block that protein from doing its job of killing cells,” said Dr. Lessene.

It took years, as the team filtered out molecules that were clearly wrong, developed a shorter list that had some impact, and ultimately landed on one that appeared to do the job.  

The research demanded patience and persistence. As they worked on a previous project that was a prelude to the more recent paper, it seemed like their search had hit a brick wall. Dr. Dewson said they were on the verge of wrapping up the project.

“And then, literally, I think a week after that, a very experienced researcher showed us a piece of data that was just black and white. And everybody thought, OK, something’s going on here. And that really led us to really continue this work further,” he said.

They published a paper in 2019, then built upon that work to bring them to their more recent discovery. Although it is significant, the scientists stress that there is a long way to go before any treatment could be offered.

They plan to continue with further explorations of these kinds of compounds, searching for one that ultimately could be developed into a safe and effective drug that could go to a clinical trial.

“We are going to push it as much as we can,” said Dr. Lessene. “But the costs of discovery of developing a drug are very, very high, so we know that we need to have more investment into the project from funders who can then really help us progress that project all the way to the clinic.”

It is a challenge familiar to scientists around the world.

“The translational part is where the chasm is. To get it from the lab into people,” said Dr. Saskia Sivananthan, Co-Founder of the Brainwell Institute.

“But it’s hopeful and always promising to learn more about the underlying mechanisms. It’s another piece of the puzzle.”

A puzzle that will demand a broadly based effort to solve, said Dr. Lessene.

It’s important to consider that neurogenerative diseases like Parkinson’s and dementia are hugely complex and they’re not going to be solved by a single biologist, geneticist, or chemist. You need all of those disciplines and more to come together and work together effectively, and you need to bring those together with clinicians.

The work has a particular relevance for Dr. Dewson, whose father was recently diagnosed with Parkinson’s.

“It may not have been the original incentive to do the research, but it does genuinely inspire the research we’re doing and makes sure we are asking the right questions,” he said.

“Working with people with lived experience of Parkinson’s ensures it’s not about just getting the next piece of data or the next grant funding. It’s about maintaining that goal of having an impact – whether it’s a new diagnostic or a new drug – that’s going to positively impact people with those diseases.”

Source: Mind Over Matter 22