In advance of World Sepsis Day, Imperial and MicrosensDx announce a collaboration to develop a more effective test for the devastating disease.

A diagnostic test that will better predict the severity and recovery from sepsis is the goal of a research collaboration just beginning at Imperial. It brings together Professor Manuel Mayr’s group in the National Heart and Lung Institute with the Cambridge-based diagnostics company MicrosensDx.

Sepsis occurs when the body’s defences against infection go wrong and start adversely affecting the way organs function. In some people this turns into septic shock, a dramatic drop in blood pressure that can damage the lungs, kidneys, liver and other organs. In severe cases, this results in death. World Sepsis Day, on 13 September, aims to raise awareness of this devastating disease.

Prompt treatment of sepsis can make all the difference, but the early stages are hard to spot and it is difficult to know which cases will respond to treatment and which will become life-threatening.

“There is a need for better biomarkers that have the ability to stratify individual sepsis patients according to their disease severity in a dynamic and timely fashion,” explains Professor Mayr, who is the British Heart Foundation Professor for Cardiovascular Proteomics and co-director of the BHF Centre of Research Excellence at Imperial. “This highlights an important clinical need for a test that can guide treatment strategies.”

The collaboration with MicrosensDx aims to develop a test that will fill this gap. “We hope that this project will establish an innovative predictive test for sepsis, enabling earlier and more precise treatment decisions to be made,” says Simon Walker, Chief Executive of MicrosensDx.

Monitoring inflammation

The focus of the project is a protein called Pentraxin 3 (PTX-3), one of the many hundreds of substances produced when the body’s immune system kicks into action. Professor Mayr’s research has shown that PTX-3 undergoes a series of modifications as it plays its role in the immune response, and that one particular modification is closely associated with the appearance and severity of sepsis.

“Modifications regulate protein function and PTX-3 is known to interact with the complement cascade,” says Professor Mayr, referring to the complex series of events in the immune response. “We have found evidence that in sepsis this interaction can become dysregulated and is associated with poor outcome.”

The collaboration with MicrosensDx, a company specialising in diagnostic systems involving nucleic acids and proteins, aims to develop a test for this modified form of PTX-3 and to assess its effectiveness in the lab using samples gathered from sepsis patients. This will demonstrate whether or not the concept of the test is sound. Further work will then be required to develop it into a test that can be used in clinical settings.

“Monitoring the protein modifications could be informative in two ways, tracking both the severity and the resolution of the inflammation,” Professor Mayr says. “We hope the test, which is still in its first stages of development, could one day offer valuable insights when treatments are not effective.”

Potential benefits

“Sepsis is an awful condition that can escalate quickly, yet often goes undetected,” says Mr Walker. “This test could potentially fill a critical gap in patient management, offering clinicians a specific, quantitative diagnostic and prognostic solution to help prioritise appropriate treatment.”

This project is a very important springboard to future collaboration. Simon Walker CEO, MicrosensDx

He sees the present project with Imperial as just the beginning of a process that could bring the test into use in emergency rooms and other critical care situations, and possibly in other care and wellness settings. “This is a very important springboard to future collaboration,” he said.

For Professor Mayr, a specialist in heart function rather than immunology, the project is also a vindication for curiosity-driven research. “We initially set out to understand how sepsis affects cardiac function, but in the process, we discovered this biomarker,” he says. “The outcome of research may be unpredictable, but it often yields valuable insights in unexpected ways.”

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