Imma Perfetto
Cosmos science journalist
A researcher finding existing drugs to repurpose for treating psychiatric disorders and chronic fatigue syndrome is amongst the winners of the 2024 Australian Mental Health Prize.
The awards celebrate individuals who have made significant impacts in mental health through cultural security, lived experience, professional innovation, and community support.
Michael Berk, Director of the Institute for Mental and Physical Health and Clinical Translation (IMPACT) at Deakin University, was recognised in the Professional category for his work transforming the treatment landscape of psychiatric disorders.
“If you look at the gap between public health burden and the research activity to develop novel therapies, it’s very large in mental health,” Berk said in an interview with Cosmos.
New treatments are urgently needed, but Berk says a problem in the field of mental health is a lack clear understanding of the pathophysiology of the major mental disorders.
“We don’t have the molecular targets that we would like to have in order to synthesise entirely novel medications,” he says.
Searching for, discovering, and taking to market new small molecule drugs is also an extremely expensive process with very high failure rates.
Instead, Berk and his colleagues – including IMPACT Co-Director Ken Walder, who leads the Novel Treatment Discovery Theme – are using stem cell technology to find and repurpose medications already in widespread use.
“The beauty of this is that the major reason for failure in drug development is safety … so we bypass that,” says Berk.
“Also, most of the drugs we’re looking at are available, off patent, cheap, so the barrier to use is very low – if we can find a drug that works.”
To do this, the team takes a patient’s stem cells and turns these cells into 2-dimensional cultures of glial cells and neurons, which mimic elements of the patient’s brain.
In a drug likeness screen, researchers then take a cocktail of 4 medications already used to treat the disorder (but which work in very different ways) and study their net-effect on the cells.
“We give these medications, and we look at which genes get upregulated and which genes get downregulated. Then we look at the most affected genes and we come up with what we call our ‘gene expression signature’,” explains Berk.
“We look at what other medications out there do the same, and we can come up with a list of drugs that are that are most similar to our combination.”
And in a disease reversal model, the patient’s cells are treated with medications to see which drugs alter their gene expression signature to more closely resemble those of normal cells.
“If a medication works on both, we like it twice as much,” says Berk.
“If you find a drug that holds up to pre-clinical testing and it holds up to epidemiological testing, you then have a viable candidate that you can take to clinical trials.”
It’s an approach which has already proven effective for multiple drugs – including a blood pressure medicine (Candesartan) for bipolar disorder, and statins and metformin for anti-depressant properties.
Most recently, the team discovered the drug trimetazidine could prove to be a game-changer for people with chronic fatigue syndrome. The medication works by increasing energy generation in the mitochondria of the cell and is listed in the World Anti-Doping Agency’s (WADA) List of Prohibited Substances and Methods.
“What’s interesting is that it only enhances energy generation under load and if there’s abnormality. It doesn’t do it at rest, which is a very desirable effect of the medication because you don’t want it to rev you up the way that amphetamines do,” says Berk.
“We think that this is going to be attractive [for chronic fatigue syndrome] because it is essentially an energy problem, and we have an energy treatment. We’re still going through the regulatory approval processes, and hopefully we’ll be able to start up a pilot study fairly soon.”
Berk was 1 of 4 recipients recognised for their work by the Australian Mental Health Prize today, including Dr Marilyn June Anderson who was awarded for dedicating more than 25 years of service at Lifeline and leading initiatives that have trained over 40,000 individuals.
Professor Juli Coffin, an Aboriginal researcher dedicated to improving the social and emotional well-being of Aboriginal youth, was recognised for creating the Yawardani Jan-ga Equine Assisted Learning program which offers a culturally grounded alternative to conventional therapies.
And Dr Louise Byrne, a pioneering advocate in the Lived Experience movement, was celebrated for her groundbreaking 15-year research program which established a comprehensive evidence base that promotes the value of Lived Experience.
