A naturally-occurring protein in the human body could protect people from one of the world’s biggest killers – sepsis. The protein’s ability to reduce inflammation in a preclinical study raises hopes that it could be the first new, natural anti-inflammatory discovered in 70 years.
The landmark study, which has been published in Endocrinology, was carried out by Adelaide University and the Central Adelaide Local Health Network. The team of researchers found that restoring depleted levels of the protein, known as corticosteroid-binding globulin (CBG), reduced relative mortality in an animal model with septic shock by more than 70 per cent.
“The results from our preclinical study were remarkable and show our therapy has the potential to reduce sepsis-related deaths significantly,” said lead author Dr Stewart Ramsay, a Research Fellow from Adelaide University’s School of Medicine.
“This is a huge step forward in the search for a new treatment for sepsis and in particular septic shock, which accounts for more than 20 per cent of all global deaths.”
CBG is a protein produced in the liver. It is responsible for moving the stress hormone cortisol around the body through the blood system.
The Adelaide group has spent 13 years investigating CBG, finding deficiency is associated with critical illness severity and ultimately a threefold increase in the risk of death in intensive care patients with septic shock at the Royal Adelaide Hospital.
“In our most recent preclinical study, we saw marked protection from sepsis progression, with a significant reduction in hypotension and organ damage,” said senior author Associate Professor Richard Young, a Senior Research Fellow at Adelaide University and the South Australian Health and Medical Research Institute (SAHMRI).
“This suggests that CBG is triggering an anti-inflammatory response unrelated to the protein’s known function in the body, reinforcing our view that it could be the first new, natural anti-inflammatory discovered in more than half a century.”
Sepsis is a life-threatening condition that occurs when the body’s immune system goes into overdrive while fighting an infection. When it is severe, it can lead to septic shock, causing blood pressure to plummet and multiple organs to fail.
Sepsis is a global health priority by the World Health Organisation, and researchers expect incidents to rise with advances in invasive surgery, implantable devices and immunosuppressive therapies.
“Septic shock urgently requires new treatments. Despite the high mortality rate, there have been no new septic shock therapies introduced into clinical practice for decades and the treatments that we do have come with limited success,” said co-author Professor David Torpy, who is a Professor of Medicine at Adelaide University and Head of the Royal Adelaide Hospital’s Endocrine and Metabolic Unit.
“This natural therapy has the potential to save lives in patients with sepsis and septic shock, with minimal toxicity.”
The team, in collaboration with Dr Jessica Lee, the commercialisation manager for the project at AusHealth, have CBG in production for first-in-human clinical trials.
“We are hopeful that this natural therapy has benefits that extend beyond sepsis to patients with severe burn injuries and other conditions where CBG is severely depleted,” said Dr Ramsay.