Australian scientists make groundbreaking septic shock discovery
Team identifies the first natural anti-inflammatory agent since cortisone was found in the 1940s
In a world-first, an Adelaide team has discovered a naturally occurring blood protein – a type of corticosteroid-binding globulin (CBG) – that could significantly decrease mortality caused by septic shock.
The CBG project is a collaboration between the University of Adelaide, the Royal Adelaide Hospital and SA-based medical research charity AusHealth.
Septic shock is an often-fatal infection that causes uncontrolled inflammation in the whole body.
“Current treatment involves antibiotics and supportive measures such as fluids, ventilation and blood pressure-elevating drugs,” says Professor David Torpy, head of the CBG project. “But the mortality is still high, leading to death in 30 to 50 per cent of patients.”
Twelve years of research has led to the identification of a type of CBG which the team is now developing as a revolutionary therapeutic treatment.
“This is the first potentially deliverable, natural anti-inflammatory agent discovered since cortisone was found in 1949,” says Professor Torpy.
CBG is a large molecule responsible for transporting a single (and much smaller) molecule of cortisol, an anti-inflammatory steroid that our bodies produce in times of stress.
Reasoning would suggest that an injection of cortisol would reduce uncontrolled inflammation brought on by septic shock and reliably reduce mortality – however this has proved not to be the case.
During a seven-year project, Professor Torpy’s team discovered it was the presence of the transporter – the CBG – that directly correlated with the severity of a patient’s illness.
“We observed that the more critical the patient, the lower their levels of CBG,” he says.
“CBG is a big and complex molecule and there are lots of dynamic things about it. I always thought it seemed to too complex and dynamic to simply be a taxi for cortisol…”
Two years ago, the CBG team at the University of Adelaide and the RAH began trials in mice at SAHMRI, headed by Associate Professor Richard Young. “We were able to significantly reduce mortality in mice,” says Professor Torpy. “The results were striking – a truly profound result.”
Professor Torpy says mice react the same as humans to septic shock and he’s ‘very confident’ the outcome can be demonstrated in a human clinical trial, anticipated to start in mid-2026.
Before that can happen, however, the team needs to produce sufficient quantities of the optimal form of CBG.
In February, the team was awarded $1.4 million from the Health Services Charitable Gifts Board to produce the CBG protein at scale in order to prove its efficacy to treat septic shock in humans.
The funding will go in part to manufacturing CBG using Chinese hamster ovary (CHO) cells.
This will be another first for the team: CHO cells are used to produce as much as a tonne of genetically engineered monoclonal antibodies (used in cancer and immune treatments) per annum – and Professor Torpy anticipates production of the natural CBG protein to be no less successful, delivering CBG at scale and more cheaply than the present means of production.
The professor and his team are being assisted by AusHealth to patent the CBG protein and commercialise the new therapy.
“AusHealth has helped tremendously with navigating the transition of CBG from research to technology,” says Professor Torpy. “Most scientists are not expert in this transition.”
He adds that it’s ‘entirely appropriate’ that this novel discovery is being commercially developed in Adelaide since the discovery work was done in that city.
“In 1923, University of Adelaide biochemist Professor Brailsford Robertson was one of the first in the world to produce insulin and treat patients. However, insulin production came into international scale in Denmark and the United States, despite first discovery in Canada.
“I’d really like to see the production of CBG become an Australian contribution. Adelaide could be producing CBG for the world.
“In America alone, hospitals spend US$38 billion annually to treat septic shock. If this clinical trial works even half as well as it works in mice, it would still save half of that expenditure per year.”