Project description
Gene-based approach against chronic kidney disease
Chronic kidney disease (CKD) is a complex heterogeneous condition associated with progressive loss of kidney function and affects millions of people worldwide. Various studies underscore the heritability of CKD through the identification of associated genetic loci. However, these genes cannot explain all cases of susceptibility to CKD. The mission of the EU-funded GeneCKD project is to identify the genetic basis of CKD and unveil the causal pathways of the disease. Emphasis will be given on the kidney-specific protein uromodulin and the design of novel interventions for counteracting the toxic effects of aberrant uromodulin expression. Results will assist early diagnosis and pave the way towards gene-based therapy of CKD.
Objective
Chronic Kidney Disease (CKD) is a public health challenge affecting millions globally. Patients have increased risks of mortality, morbidity, and progression to end-stage kidney disease (ESKD). CKD is often clinically silent, disease mechanisms are unclear and targeted therapies are unavailable. Recent studies support considerable contributions of underappreciated monogenic aetiologies in adults with CKD, suggesting that most inherited kidney diseases remain undiagnosed, untreated and poorly understood. Our overarching objective is to unravel the genetic basis of CKD towards early diagnosis and gene-based therapy. We therefore established the Israeli ESKD genetic cohort and already recruited clinical data and samples from 2,000 participants with ESKD. Our main objectives are: 1) to unravel known and novel CKD genes by interrogating high-risk groups for genetic CKD using next generation sequencing on a population level; 2) to study novel monogenic CKD disease mechanisms by using patient-derived kidney organoids and mutation-specific mouse models. Specifically, we will study a newly identified WDR19 mutation leading to many adult onset-ESKD cases in the Israeli Arab-Druze population; and 3) to develop gene-based targeted therapies for CKD. We will focus initially on monogenic CKD secondary to gain-of-toxic-function mutations in UMOD (encoding uromodulin, a kidney-specific protein). This relatively frequent adult CKD aetiology accounts for 0.5-2% of CKD cases worldwide. Altered uromodulin?s toxic effect is suitable for novel RNA-based therapies. Gene silencing of uromodulin with antisense oligonucleotides will be performed and studied, using a patient-derived in vitro model as well as a Umod mouse model. This project will improve CKD classification and clinical management, reveal disease mechanisms as well as novel treatments. In a broader perspective, this project will set the stage for future clinical trials and for other RNA-based gene-specific CKD treatments.
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 biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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 - HORIZON ERC 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-2021-STG
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52621 Ramat Gan
Israel
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