Project description
Small molecules could ameliorate or prevent pancreatitis simply and cost-effectively
The incidence of acute pancreatitis – a serious inflammation of the pancreas most often associated with excessive alcohol use or gallstones – is increasing with serious consequences for patients and national healthcare systems. Available treatments are limited. FGF21, a protein predominantly produced in and secreted by the liver, may lessen acute pancreatitis in mice. Its expression increases with increasing RORα transcription factor. The ERC-funded PanRORα project aims to investigate whether RORα agonists (substances that act like or amplify RORα activity) that also increase FGF21 expression can treat acute pancreatitis. In addition, the team will evaluate whether the agonist can prevent acute pancreatitis caused by an endoscopic procedure used to examine pancreatic ducts.
Objective
Pancreatitis in humPancreatitis in humans is a cause of significant morbidity and mortality. Acute pancreatitis events have increased worldwide over the last 20 years at an average annual percent change of 3% and the economic burden is growing (1). Treatments for pancreatitis are currently limited. The overall mortality rate in acute severe pancreatitis is 10-15%. Thus, a specific treatment for pancreatitis is of great need. Recent reports suggest that FGF21 can ameliorate acute pancreatitis in mice. FGF21 is a protein which belongs to the fibroblast growth factor family and is predominantly produced and secreted by the liver. FGF21 is positively regulated by the ROR transcription factor. I will assess whether a ROR agonist that we identified by screening compounds that act against Non-Alcoholic Steatohepatitis (NASH) in mice, and which we found to increase FGF21 expression, can be used to treat acute pancreatitis (2). In addition, we will also investigate whether increased FGF21 expression can be used to prevent pancreatitis triggered by Endoscopic Retrograde CholangioPancreatography (ERCP). We established the Caerulein and alcohol induced pancreatitis models. In the Caerulein model we show [unpublished and patented (US Pending Patent 11,865,090)] significant therapeutic effects of a small compound that activates ROR. In this PoC, we intend to explore new compounds of the same family with better efficacy on FGF21 in vivo, and improve the treatment for acute pancreatitis. This study will establish FGF21 as a prognostic biomarker for acute pancreatitis in humans, by plasma ELISA and circulating free DNA. This PoC project has the potential to achieve a breakthrough therapeutic treatment for acute pancreatitis; one that is commercially viable, effective, avoids an immune response and has the benefits of a natural delivery, a natural chemical composition of FGF21, lower cost, higher availability, simple storage and overcomes the short half-life of synthetic proteins.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences chemical sciences organic chemistry alcohols
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
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91904 JERUSALEM
Israel
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