Descrizione del progetto
Affrontare le morbilità acquisite in terapia intensiva
L’unità di terapia intensiva svolge un ruolo fondamentale nella prevenzione della morte dovuta a condizioni gravi come sepsi, interventi chirurgici complicati o traumi estesi, fornendo un supporto vitale agli organi. Tuttavia le degenze prolungate in terapia intensiva spesso comportano comorbilità come insufficienza d’organo persistente, debolezza muscolare e dipendenza dai ventilatori. Il progetto AdrenalWeakness, finanziato dal CER, si concentra sulla potenziale associazione meccanicistica tra la debolezza muscolare acquisita in terapia intensiva e l’insufficienza surrenalica, un’ipotesi di lavoro mai esplorata prima. L’approccio di ricerca sperimentale e clinica di AdrenalWeakness mira a identificare e testare composti in grado di affrontare contemporaneamente queste comorbilità, evitando effetti collaterali dannosi e migliorando gli esiti del recupero.
Obiettivo
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.
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
3000 Leuven
Belgio