The University of Oxford today announced a partnership with Danaher Corporation to develop a new test to enable precision medicine care for sepsis, a pathological immune response to infection that accounts for one in five deaths globally each year.
The test will build on research from the laboratory of Julian Knight, a professor of genomic medicine at Oxford and leading expert in sepsis biology. The novel test will leverage rapid molecular diagnostic technologies provided by Cepheid, a Danaher subsidiary, to pinpoint different subtypes of sepsis and allow the development of novel personalised care paths including which targeted therapies are most likely to help.
Sepsis is a serious condition that occurs when the immune system fails to react normally to an infection and damages tissues throughout the body. If left unchecked, it can lead to complete organ failure.
Currently, doctors cannot accurately predict which patients are most likely to develop sepsis after an infection, nor can they determine which early-stage cases of sepsis are most likely to become severe or life-threatening, and by what mechanisms of immune dysfunction.
However, recent research by the Knight group has shown how molecular approaches based on measuring RNA from white blood cells can identify a specific immune response associated with poor outcome that could benefit from drug intervention.
Being able to subtype sepsis in patients at the molecular level could have many potential clinical benefits, such as enabling doctors to choose suitable therapies and treatment settings. It could also help pharmaceutical companies choose appropriate patients for clinical trials of new or previously developed therapies.
Julian Knight, Professor of Genomic Medicine at the University of Oxford’s Nuffield Department of Medicine, said: “We are delighted to be partnering on this innovative project. We believe this will accelerate progress to a precision medicine approach for sepsis in which we can rapidly identify and treat patients with a particular sepsis response state. We hope the test will help clinicians to choose the right therapy, maximising benefit and minimising harm for the individual patient.
“In our research, we have used a molecular approach to try to understand if there are particular sub-groups of patients that might benefit from specific interventions. We now have a way of measuring the expression of a small number of genes, which allows us to estimate the likelihood of a worse outcome – a sepsis response signature.”
Professor Knight (pictured left), whose work is supported by the NIHR Oxford Biomedical Research Centre (BRC), whose Genomic Medicine Theme he leads, added: “Current methods – using RNA sequencing and other gene expression measurements – take days or even weeks to carry out and analyse. Given that patients with sepsis can deteriorate very quickly, this is too long to be used clinically. The partnership will work to develop a point-of-need test designed to indicate within about an hour which group a patient is in. If we could rapidly categorise patients in this way with an easy-to-use test, we could then run clinical trials using potential treatments.”
The Cepheid test will be based on a sample-to-answer, real-time PCR system capable of rapid, multiplexed molecular diagnostics, designed to yield results at high accuracy within minutes.
The collaboration with Oxford is part of Danaher’s Beacon programme, which funds pioneering scientific research carried out in academic settings. The ultimate objective of the programme is to develop innovative technologies and applications that can improve human health. The Beacon programme’s focus areas include genomic medicines, precision diagnostics, next generation biomanufacturing, human systems and data sciences.
Vanessa Almendro, VP, Science and Technology Innovation, Danaher, said: “We are excited for Danaher and Cepheid to collaborate with the University of Oxford on innovating new diagnostic approaches to make sepsis – one of the most life-threatening conditions – more clinically actionable. From potentially enabling precision medicine and smarter clinical trial design, to ensuring that patients are cared for in the proper settings, this work could ultimately make a difference for millions worldwide.” As well as the NIHR Oxford BRC, Professor Knight’s work has been funded by the Medical Research Council and the Wellcome Trust.