NEW YORK (360Dx) – Diagnostics firm Prenosis continues to progress in its sepsis test development program, with research published this month in Nature Scientific Reports demonstrating the utility of protein biomarkers in combination with patient medical records to detecting the condition.
Launched as a spinout from the University of Illinois in 2014, Prenosis has targeted sepsis as the primary focus of its test development program. Work published this summer in Nature Communications used measurements of CD64 levels on neutrophils to make early diagnoses of sepsis. The most recent study expands those efforts to look at 15 potential protein biomarkers, including neutrophil CD64 (nCD64).
Using a Luminex immunoassay system to analyze 444 patients hospitalized between May 2014 and May 2016 and for whom physicians had ordered blood cultures, the researchers identified six markers — IL-6, nCD64, IL-1ra, PCT, MCP1, and G-CSF — that identified patients in the early to peak phase of sepsis with an area under the curve of .80. Combining that panel with patient electronic medical record (EMR) data, the test achieved an AUC of .81. The EMR data by itself managed an AUC of .75.
The authors also noted that measurement of the six markers at a single time point provided the same predictive power as collecting EMR data over the course of 16 hours, indicating that such a panel could prove useful for early detection of sepsis, allowing for earlier and potentially more effective intervention.
The study is not conclusive regarding the effectiveness of the biomarker measurements, said Ruoqing Zhu, assistant professor of statistics at the University of Illinois at Urbana-Champaign and senior author on the study, noting the recent paper "is really just the first stage of the entire pipeline."
Zhu, who is not employed by Prenosis, said, however, that the data indicates that biomarkers can provide useful information beyond that contained in EMRs, and that "we should definitely pursue that direction."
He and his collaborators at Prenosis are now planning additional studies that will look at larger panels of markers in broader sets of patients across more time points. Currently, they are putting together a multi-site study that aims to measure a hundred to several hundred potential markers in several thousand patients, Zhu said.
The hope, he added, is that this work will help the researchers not only diagnose sepsis earlier but also better define the disease and possibly subtypes.
"The definition of sepsis is not really that accurate as it is used in practice," he said. "So, we are looking at how these biomarkers could categorize patients into different clusters, and then whether those clusters provide any interesting information that relates [to the disease process and outcomes]."
While the study will be conducted using a Luminex immunoassay platform, the plan is to ultimately arrive at a panel small enough to run on Prenosis' point-of-care device, Rhu said. As the company previously noted, it has developed a prototype POC device that it envisions could be used for early sepsis detection in hospitals and doctors' offices. It has said it hopes to launch an initial version of the test in the next two to three years.
The device is based on microfluidics and biosensor research conducted in the lab of Rashid Bashir, a professor of bioengineering at the University of Illinois and the chief scientist and co-founder of Prenosis. It consists of a biochip containing modules for cell lysing, electrical counting, and immune-affinity capture of target molecules.
In the earlier Nature Communications work, the researchers used the device's electrical counting functionality to count white blood cells and the immune-affinity portion to capture and measure levels of neutrophil CD64 expression.
The immune-affinity portion can also be functionalized with antibodies to different markers, allowing the company to expand the molecules measured in its test if future studies indicate it could improve sepsis diagnosis.