Technology Overview:
A global, unbiased, cardiac tissue-based proteomics approach for biomarker discovery in a mouse model of sepsis identified pentraxin 3 (PTX-3) as one of the most differentially expressed proteins in cardiac tissue from septic mice. PTX-3 accumulated as an octamer due to disulphide-bond formation, most notably in heart, aorta, kidney and lung. Octameric PTX-3 was detectable in mouse serum.
A proof-of-principle clinical study was conducted with serum samples from 31 sepsis patients admitted to the ICU. On admission to the ICU, there was no difference in octameric, tetrameric and monomeric PTX-3 between those who ultimately survived (survivors) and those who died (non-survivors). Over a time course of 11 days, however, reduction of octameric PTX-3 to its monomeric form was associated with a greater survival after 28 days of follow-up. For example, on day 2 post admission there was a statistically significant difference between the two groups, where octameric PTX-3 was undetectable in survivors, but still constituted more than half of total PTX-3 in non-survivors. Levels of tetrameric PTX-3 were similar in the two groups. In comparison to the conventional measurements of total PTX3, the redox-sensitive oligomerization of PTX3 was more dynamic and a superior predictor of disease outcome.
Applications:
Severe sepsis and septic shock are major healthcare problems associated with high levels of mortality, affecting millions of people around the world each year, and increasing in incidence. Medical care of sepsis patients combines prompt treatment with antibiotics and supportive care and often requires artificial organ support provided in an intensive care unit (ICU). However, despite all efforts, sepsis is fatal in 30-40% of sepsis patients in the ICU. Hence, there is a high demand for specific biomarkers that enable clinicians to quickly and accurately categorize patients according to their prognosis and response to therapy, enabling alternative treatment/interventions to be implemented earlier where necessary.
Prof. Mayr’s group have demonstrated in a proof-of-principle study that changes in the oxidation state of the acute phase protein, pentraxin 3 (PTX-3) are associated with the early identification of severely septic patients not responding to treatment, at high risk of acute organ failure and death, and where a change or intensification of therapy is required to reduce the risk of acute organ failure and death.
Benefits:
Earlier identification of patients not responding to treatment enabling earlier alternative clinical interventions and reducing the time to effective treatment will improve clinical and economic outcomes by reducing mortality, morbidity and hospital length of stay.
The sepsis market is well defined and offers a clearly defined route to market for the PTX-3 product. As a prognostic marker for disease progression and response to therapy the total addressable market for PTX-3 has been estimated to be $200m in the US and Europe and other selected markets, representing one of the largest market opportunities for a diagnostic test.
Opportunity:
This technology is available for exclusive licensing to a commercial entity active in the market space.
IP status:
PCT Pending (Priority Date: 24/05/2013)
Keywords:
Cardiac tissue-based proteomics approach, Oxidised pentraxin 3, Prognostic marker, PTX-3, Severe sepsis, Septic shock