Could diagnosis of brain injury be as simple as a blood test?
Early detection
In Australia when you turn 50, a national program sends you a free, simple test to screen for bowel cancer – when detected early, 9 out of 10 cases can be treated successfully. So, imagine then, if a similar type test could be done for dementia, the second leading cause of death in Australia. It could mean that many people receive early treatment, and when combined with constantly improving medications, may never even develop symptoms.
“The problem currently is by the time patients hit the clinic, they're quite symptomatic. And the disease has probably progressed for 10 plus years before they've gotten there. So if you have a cheap, accessible way to detect these changes before symptoms appear, you can effectively apply therapy early and avoid that disease.”
That’s a long-term desire for Dr. Zac Chatterton, lecturer at the University of Sydney’s Brain and Mind Centre. His primary research focus is epigenetics – the study of how behaviours and environment can cause changes that affect the way your genes work.
His team is accurately detecting little fragments of DNA that come from brain cells undergoing cell death. With detection, they’re able to create a test applies across neurology for a variety of diseases. It also means they can start profiling what's going on in the brain with a simple blood test.
Dr. Chatterton is currently working with the Royal North Shore hospital trauma unit to apply this test to a small cohort of trauma patients. Some people might have a mild traumatic brain injury (TBI) and aren’t showing signs of direct neurological damage. By determining the level of injury with a blood test, they can forego any CT scan and radioactive exposure.
In more severe TBI, it can be hard to know where in the brain trauma has occurred because the resolution on an MRI or any other neuro imaging device is quite coarse. But Chatterton’s work with blood is on a molecular level, so they’re able to detect individual cells that are undergoing degeneration, pinpointing the exact location in the brain.
Zac completed his first qualification in cancer biology, but his experience with cancer-based biomarkers got him thinking about translating this work when he transferred to neuroscience – attracted by the possibility that the cell free DNA assays being developed in cancer could work in neurology.
Collaboration and international interest
Chatterton’s team recently collaborated with the US Navy, and the Walter Reed Hospital, to look at the effect of explosive device exposure. They were able to draw personnel bloods prior to and after exposure to explosions. The team found fragments of brain-derived DNA were within patient's blood, after they were exposed to these pressure changes, and showed spikes in these fragments of neuron and glia - DNA of the brain.
This cross-institutional collaboration inspired a computational approach for storing/analyzing epigenomic data that was subsequently patented. This made the current blood test possible; and funding from the CDIP grant helped commericalise this approach, making it more accessible.
He also worked with the intensive care unit at Royal North Shore Hospital in Sydney on a study labelled the Neuro-K study. His collaborator there, Intensive Care Specialist Anthony Delaney has an interest in severe brain injury, and in research.
"At present, we have very crude tools to estimate the extent of brain injury for patients with acute severe brain injury. The Neuro-K study results will help build the platform to enable clinicians to provide individualised care for patients based upon a more detailed understanding of the extent of their acute brain injury.
“This information will also help clinicians provide better information to patients and families so that they can understand the extent of their brain injury and the implications for their prospects for recovery and their future."
The ‘valley’ of mid-career research
Like many early and mid-career researchers Dr Chatterton’s challenges are far beyond the lab. In order to obtain funding, you need to be a cited researcher, and in order to be a cited researcher, you need to be published. But dedicating time to publishing means you may miss out on other, impactful commercialisation opportunities for your research.
With support from the university’s CDIP grant, Zac's team is now able to analyse every single cell of the human brain for cheaper than anyone else. Researchers know this has broad applications for other types of disease that affect the brain. But how do you go about selling research to potential funders when you can’t yet specify or quantify those applications?
Dr Chatterton says it is vital to support discovery into the critical, yet unknown outcomes, but extremely challenging to explain those unknowns in grant applications.
“The fact that we still don’t know how DNA is regulated in the human brain is dumbfounding! We have so much to explore."
Discovery, diagnosis and prevention
Securing funding for 'unknowns' is a particular challenge for discovery scientists, yet searching for unknowns is the crux of basic research. While it's often hard to predict how research will evolve into a clinically translated product or where that's going to occur , the outcomes of his blood test have been driven by basic science, as he strives to understand differences in brain chemistry..
Zac hopes his research in understanding epigenetics of the human brain will assist in understanding what processes precede disease.
“Once we understand this we can prevent a lot of diseases, particularly chronic neurological diseases, from actually occurring."
Within the next 10 years, he believes epigenetics has a large role to play in creating new diagnostics for a range of diseases using cell free DNA, and this will assist drug design and development in disease prevention.