His team in the Bardy Lab, based at the SAHMRI building in Adelaide, grow and age live brain cells from patients with complex neurological disorders to unlock the mysteries of such medical riddles as childhood dementia, Parkinson’s disease and brain cancer.
“The work we are doing has the capacity to fast-track solutions for people with brain disorders,” says Associate Professor Bardy.
“It is really exciting to be able to design and test solutions to help people. The stakes are high. Patients diagnosed with neurological diseases are often facing their most vulnerable life moment, and they desperately need better treatment options.”
After pioneering experimental models of human brain tissue from patients in petri dishes for six years at the prestigious Salk Institute in California, Associate Professor Bardy was recruited by Flinders University and SAHMRI in 2017 to bring his innovative line of research to Adelaide.
Progress within the Bardy Lab marks the culmination of a whirlwind five years for the French-born researcher, whose approach to examine brain cancer and neurological disorders with patient-derived tissue has enabled an exciting pre-clinical research pathway and the hope of new translational opportunities.
Along the way, one of Associate Professor Bardy’s great breakthroughs was creating a new type of culture medium that allows human neurons to survive and thrive in a laboratory environment – an entirely different medium to that which sustains animal cells and non-neuronal cells.
“Working with human cells rather than animal cells is very different and required the design of a whole new complex experimental model”. He admits that he got stuck several times wondering how to arrive at the right solution.
“One challenge was that human neurons in the lab need a medium comprising specific concentrations of more than 70 compounds to mimic the human brain functions, so finding the right combination was a bit like trying to crack a code with a million possibilities.”
Without the resources or time to test every possible combination, Associate Professor Bardy started with calculated guesses, based on his detailed observation of brain tissue.
“I didn’t get it right the first time, but after some effort we soon had a working formula.”
He had invented BrainPhys, a neuronal medium that is now widely used to culture and mature active human neurons in vitro.
Associate Professor Bardy says it has provided the necessary key to unlock new possibilities across many areas of brain disease research – with the Bardy Lab researchers now simultaneously studying a form of childhood dementia, Parkinson’s disease and brain cancer.
“We can look at the intricate function of brain cells and how they communicate with each other within a neural circuit that resembles the human brain,” he explains.
With the recent boost of $1 million in funds from the Michael J Fox Foundation, Shake It Up Foundation and The Hospital Research Foundation, resources are in place for a rapid acceleration of testing drugs on the laboratory cells before enrolling clinical trials.
“In Parkinson’s disease, we’ve noticed the energy levels in cells taken from patients drop much quicker than those from healthy subjects of the same age,” says Associate Professor Bardy. “Therefore, we are trying to come up with new and creative ways to restore the energy in those cells.”
He is also seeing great progress with cells taken from 10 children with a form of early-onset dementia.
“We reprogrammed the skin cells from these kids into brain cells, which we can study in the greatest molecular and physiological detail in the laboratory without the ethical limitations of clinical research.
“We can see specific differences from the neurons of the kids with dementia compared to healthy kids of the same age. Our research team is now gearing up for swiftly testing which drugs could reverse this condition, without putting the patients at risk during the trials.
“For the brain cancer study, we have worked closely with local neurosurgeons for the last few years and examined brain and tumour biopsies from patients with about 15 months to live. Careful analyses of this tissue led us to identify a repurposed drug that appears effective in killing the cancer cells.”
Associate Professor Bardy and his colleagues are working hard now to move this discovery from the bench to the clinic. If the repurposed drug works as well in patients as it worked in the pre-clinical model, it will save countless lives around the world.
A significant aspect of the Bardy Lab’s progress is through using robotics to test drugs on the tissue samples, to increase the yield and speed but also ensure reproducibility of the results.
In the past five years, the team has also worked with local material scientists to develop a new petri dish substrate which improves on the adherence of human brain cells. It maintains complex electrical connections between neurons, allowing a patient’s brain to be modelled more accurately and therefore determine the best treatment with more certainty.
For Associate Professor Bardy, Flinders’ research ethos and progress being made in this highly specialised area of research vindicated his decision to move to Adelaide – a city he had never previously visited.
He says a critical step is still ahead – ensuring that this innovative science is translated from the lab to the world.
“I really feel that I am racing against time with this research. I know that the deterioration of a child with early-onset dementia is so severe and irreversible, which makes it imperative to find solutions that can change these children’s lives as soon as possible.
“I am constantly encouraged and inspired by our community and humbled by the resilience of people and their family facing terminal brain disorders.
“Am I satisfied? Never. I’m impatient but persistent. I know it’s a slow process but every step forward matters and I am delighted with the progress we are making. We will not give up and we will make a difference.”
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