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GeneCKD

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Deciphering the genetic basis of chronic kidney disease towards prevention and p...

Deciphering the genetic basis of chronic kidney disease towards prevention and personalized therapy 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, dise... ver más

30/06/2027

Sheba Research Fun...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT A... No se ha especificado una descripción o un objeto social para esta compañía.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-06-01

ERC-2021-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 3 años

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1 Participantes

Sheba Research Fund

1.80M€ | Lider

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Duración del proyecto: 60 meses Fecha Inicio: 2022-06-01
Fecha Fin: 2027-06-30

Líder del proyecto

MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT A... No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 2M€

Descripción del proyecto 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.

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