A biomarker molecule could be key to saving the lives of patients with sepsis, according to a team of researchers at Duke University.
Their study published in the journal Science Advances found that the molecule methylthioadenosine (MTA) can predict which patients are most likely to die from sepsis — an overblown response to infection in which the immune system attacks healthy tissue and organs.
Dennis C. Ko
The revelation, the researchers say, means clinicians may be able to regulate MTA levels to avoid severe sepsis. It could also yield other biomarkers that lead to better treatments.
“This area has been a graveyard for the pharmaceutical industry, with more than 100 failed clinical trials of therapies that target the body’s abnormal response to infection,” study researcher Dennis C. Ko, MD, PhD said in a news release.
“With better biomarkers, we may be able to group sepsis patients into more refined categories to more effectively test and possibly even resurrect old drugs.”
Ko was the lead author of a study published in 2012 in which he and colleagues sought genetic characteristics that might lead to more or less pyroptosis — the massive cell death that can occur during sepsis.
Bacteria (yellow) interact with a human white blood cell in this image from the NIAID. If left unchecked, this encounter might develop into sepsis, but a Duke team has now identified a chemical signal to predict which patients are most at risk of dying from sepsis.
They found that patients partially differed in the recycling process that creates the essential nutrient methionine, named the methionine salvage pathway. In the more recent study, Ko and fellow researchers examine the effect of MTA, a component of the process.
Their research showed that elevated amounts of MTA in plasma were associated with a higher chance of mortality. In addition, they found that MTA levels were roughly 80% accurate in predicting mortality.
That led to them to wonder whether changing levels of MTA can affect the outcome of a patient with sepsis. The researchers found that mice with Salmonella survived longer when they received the molecule before being infected.
However, Ko stressed that it will take much more research to determine whether MTA can fulfill such a role in the clinic and in humans.
“It gets very complicated very fast,” he said in the news release. “Some people might have too robust of an inflammatory response, some people might not have a robust enough response, and as a result, their MTA levels will differ, both between individuals and within an individual over the course of an illness. Biomarkers could determine where individuals fall along that continuum and what treatments might work.” – by Joe Green
Ko DC, et al. Proc Natl Acad Sci USA. 2012;doi: 10.1073/pnas.1206701109.
Wang L, et al. Science Advances. 2017;doi:10.1126/sciadv.1602096.
Disclosure: Duke University has applied for a provisional patent on using MTA as a sepsis biomarker on behalf of Wang, Dennis C. Ko, Emily R. Ko and Tsalik. No other researchers reported relevant financial disclosures.