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Innovative technologies for the development of lead candidates in the treatment of sepsis

RCSI StAR International PhD Programme Research Projects

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Prof S Kerrigan , Dr G Curley Applications accepted all year round Competition Funded PhD Project (Students Worldwide)

About the Project

Sepsis is the most common condition, and the single biggest cause of mortality, in critically ill patient. Outside of Critical Care Units, sepsis contributes to one-half of all hospital deaths. In addition, sepsis confers a major long-term economic burden on survivors and on society due to functional and cognitive disability. Improved treatment of sepsis could offer meaningful improvements in population health, quality of life and survival. In the developed world, sepsis is dramatically increasing by an annual rate of between 8-13 % over the last decade, and now claims more lives than heart attack, stroke or colon cancer and breast cancer combined. Sepsis involving multiple organ dysfunction is associated with especially high morbidity and mortality (up to 50%) and consumes a vast amount of healthcare resources.

In Ireland, the cost of treating hospitalized sepsis patients was in the region of €250 million in 2013 alone (National Sepsis Steering Committee report, 2015). These figures do not take into account the costs associated with the lifelong follow up that is required post hospital discharge (most survivors experience lifelong complications due to sepsis). This makes sepsis the most expensive condition treated in Irish hospitals. At present there is no specific anti-sepsis treatment available, therefore management of sepsis patients relies on therapeutic measures to be initiated as soon as possible after sepsis diagnosis to include administration of appropriate antibiotics, source control measures when necessary and resuscitation with intravenous fluids and vasoactive drugs when needed. Although antibiotics play a key role in fighting the infection treatment success is often poor as downstream events as a result of endothelial dysregulation is not controlled.

A January 2018 search of the revealed almost 550 trials of drugs and devices for the treatment of sepsis in various stages of completion, however no therapeutic options have made it to the market yet. It can be conservatively estimated that of upwards of $30billion has already been spent on the objective of developing a higher order therapy for the treatment of sepsis, indicating the market need. Previous approaches have focused on treating or controlling late stage pathophysiological effects (such as inflammation, thrombus formation & coagulation etc), an approach which has resulted in the failure of many compounds in clinical trials as a result of later intervention in the disease progression pathway.

This project will use cutting edge technology to identify lead candidate drugs that target very early in sepsis progression by targeting the human vascular endothelium.

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