Hope for immunocompromised patients with cirrhosis
Cirrhosis is the most common chronic liver disease. It leads to alterations of the immune system including a deficiency of the antibacterial function of neutrophils.
Our research work carried out in collaboration with hepatologists of the CRI using neutrophils from patients with advanced alcoholic cirrhosis led to the identification of major molecular deficits, particularly in the NADPH Oxidase 2 (NOX2, gp91phox) system.
This partly explains recurrent infections that are often fatal. Despite treatment with antibiotics, the mortality rate of patients is abnormally high. Thanks to an original approach based on the activation of endosomal TRL7/8 receptors with R848 (Resiquimod),
we were able to correct molecular deficits and restore a normal bactericidal activity of neutrophils from patients (Diagram below, Rolas L et Coll, Gut , 2018; Rolas L et Coll , Hepatology, 2013, Boussif A et Coll, J. Hepatol, 2016).
This strategy has also been proven in a murine model of cirrhosis with beneficial effects on bacterial infection and animal survival. This proof of concept led to a recently accepted patent in USA, which represents a great hope for many immunocompromised patients.
« METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF BACTERIAL INFECTIONS IN PATIENTS SUFFERING FROM CIRRHOSIS »(N° 10,201,536, BIO15052-US-PCT