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AdrenalWeakness

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Concomitant Reversal of Adrenal Insufficiency and Muscle Weakness to Enhance Rec...

Concomitant Reversal of Adrenal Insufficiency and Muscle Weakness to Enhance Recovery from Prolonged Critical Illness Sepsis, complicated surgery or extensive trauma cause hyperinflammation-induced critical illness which requires vital organ support in an intensive care unit (ICU) in order to avoid imminent death. Although modern intensive care h... ver más

30/09/2029

KU Leuven

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

KATHOLIEKE UNIVERSITEIT LEUVEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-10-01

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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KU Leuven

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Duración del proyecto: 59 meses Fecha Inicio: 2024-10-01
Fecha Fin: 2029-09-30

Líder del proyecto

KATHOLIEKE UNIVERSITEIT LEUVEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Sepsis, complicated surgery or extensive trauma cause hyperinflammation-induced critical illness which requires vital organ support in an intensive care unit (ICU) in order to avoid imminent death. Although modern intensive care has reduced mortality, a large number of survivors continue to require such supportive care in the ICU sometimes for weeks or months. Once in this prolonged phase, typical ICU-acquired morbidities such as lingering organ failure, muscle wasting and weakness and vasopressor- and ventilator-dependency become the main drivers of poor short- and long-term outcome irrespective of the initial diagnosis upon admission. Research from our group has focused on two of these unresolved problems, namely ICU-acquired muscle weakness and ICU-acquired adrenal insufficiency, for which there is either no treatment or treatment has deleterious off-target effects that may fuel a vicious circle impairing short- and long-term recovery. Today, intensivists see these conditions as two separate pathophysiological entities, an assumption we think is false. We hypothesize that ICU-acquired adrenal insufficiency shares upstream underlying mechanisms with ICU-acquired muscle weakness, pathways that are currently unexplored and that can be manipulated with the potential to reverse both problems together. We will test this hypothesis via an experimental and a clinical track. The proposal starts from a novel, controversial idea, developed via experiments in a unique, clinically relevant and validated mouse model of sepsis-induced critical illness and via the study of human patients, and aims to close the loop with a proof-of-concept randomized controlled trial. Our ambition is to identify and test a novel compound, or combination of compounds, to concomitantly reverse adrenal insufficiency and muscle weakness in prolonged critical illness, while avoiding deleterious side-effects and aiming for synergy. Reaching this ambitious goal would represent ground-breaking progress.

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