CE14 - Physiologie et physiopathologie

NGAL, a novel target in Hypertension and associated comorbidities – NGAL-HT

NGAL and blood pressure

«Our recent exploratory studies identified novel key roles of NGAL (Neutrophil Gelatinase-Associated Lipocalin) in the control of blood pressure. This led to the NGAL-HT consortium associating synergic expertise in pathophysiological research, translational studies and population genetics.

hypothesis and objectives

Hypothesis: NGAL is involved in blood pressure control via the modulation of renal Na transport. Moreover targeting NGAL may have several beneficial effects in CV and renal comorbidities related to hypertension. Our objectives are to 1) determine the underlying mechanisms, 2) study the correlations between plasma NGAL, NGAL polymorphisms, blood pressure and Na excretion in dedicated human cohorts and 3) study the therapeutic efficacy of new already identified NGAL inhibitors.

Combination of animal models and human studies

Ongoing

The NGAL-HT project will increase knowledge on pathophysiological mechanisms but also provide new insights in genetic aspects of blood pressure and proof of concept studies for use of NGAL as a novel therapeutic target in the field.

Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects. Barrera-Chimal J, Lima-Posada I, Bakris GL, Jaisser F. Nat Rev Nephrol. 2021 in press
Roles of Mineralocorticoid Receptors in Cardiovascular and Cardiorenal Diseases. Jonatan Barrera-Chimal, Benjamin Bonnard and Frederic Jaisser. Annual Rev Physiol, 2022 in press

brevet déposé: 1. NGAL inhibitors: PCT/EP2020/056077, filled March 6, 2020; USA 17/434,535 filed August 27, 2021

Our recent exploratory studies identified novel key roles of NGAL (Neutrophil Gelatinase-Associated Lipocalin) in the control of blood pressure. NGAL was previously identified by partners 1 and 2 as a novel mineralocorticoid target leading to experimental and clinical studies, as well as a strong patent portfolio and licensing. This unexpected effect on blood pressure control and its potential therapeutic impact led to the NGAL-HT consortium associating synergic expertise in pathophysiological research, translational studies and population genetics.

Hypothesis: NGAL is involved in blood pressure control via the modulation of renal Na transport. Moreover targeting NGAL may have several beneficial effects in CV and renal comorbidities related to hypertension. Our objectives are to 1) determine the underlying mechanisms, 2) study the correlations between plasma NGAL, NGAL polymorphisms, blood pressure and Na excretion in dedicated human cohorts and 3) study the therapeutic efficacy of new NGAL inhibitors already identified by partners 1-2.

The NGAL-HT project will increase knowledge on pathophysiological mechanisms but also provide new insights in genetic aspects of blood pressure and proof of concept studies for use of NGAL as a novel therapeutic target in the field.

Project coordinator

Monsieur Frederic JAISSER (CENTRE DE RECHERCHE DES CORDELIERS)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CIC NANCY 1433 CIC NANCY 1433
Unité de Génétique évolutive humaine
CRC CENTRE DE RECHERCHE DES CORDELIERS

Help of the ANR 455,320 euros
Beginning and duration of the scientific project: February 2020 - 42 Months

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