Project description
Membrane channel inhibitors for the treatment of liver diseases
Connexin and pannexin cell membrane channels mediate biochemical exchange between the cell and its extracellular environment. These channels were implicated in processes associated with a number of inflammatory conditions. The CONNECT project had established that peptide-based inhibitors of these channels decrease the manifestation of acute and chronic liver disease but there were stability issues. CONNECT-2-CLINIC is going to capitalise on these findings and develop stable specific connexin hemichannel and pannexin channel inhibitors for clinical applications. The new inhibitors will be tested initially in vitro and subsequently in relevant mouse models of disease. In parallel, the team will create a business plan to demonstrate market value along with a solid proof-of-concept for further pharmaceutical development.
Objective
Pannexin1 (Panx1) channels mediate the exchange of biochemical messengers between the cytosol of a cell and its extracellular environment. This type of cellular communication underlies cell death and inflammation, both which are associated with a plethora of diseases. Closing pannexin channels therefore seems an interesting therapeutic strategy. In this respect, the ERC Starting Grant project CONNECT has demonstrated that peptide-based inhibition of Panx1 channels counteracts the manifestation of acute and chronic liver disease. However, these peptides cope with stability issues thus impeding clinical application. No other types of appropriate Panx1 channel inhibitors are available today despite their promising therapeutic potential. The present CONNECT-2-CLINIC project will meet this urgent need by generating specific and in vivo-applicable Panx1 channel inhibitors. For this purpose, nanobodies targeted towards Panx1 will be produced using unprecedented protocols that combine DNA immunization with new nanodisc technology. Panx1 nanobodies will be tested in vitro for their capacity to inhibit Panx1 channels and to reduce cell death and inflammation. They will be subsequently tested in a human-relevant mouse model of cholestatic liver disease. This technology track will be aligned by a 3-phase business track in order to analyze and create market value. By doing so, the CONNECT-2-CLINIC project will provide solid proof-of-concept for further pharmaceutical development and clinical application.
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.
- medical and health sciences basic medicine immunology immunisation
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences clinical medicine hepatology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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.
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.
Funding Scheme
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.
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.
ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-PoC
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1050 BRUSSEL
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.