Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of conditions characterized by fat accumulation in the liver and a variable clinical course. Metabolic dysfunction-associated steatohepatitis (MASH) represents its more aggressive form and is characterized by chronic inflammation, hepatocellular injury, and fibrosis, with potential progression to advanced fibrosis, cirrhosis, and hepatocellular carcinoma.

The project aims to elucidate the molecular mechanisms underlying the transition from MASLD to MASH and identify new targets for the development of therapeutic strategies. To this end, the group is developing a three-dimensional (3D) cellular model that recapitulates the main features of the disease, with particular emphasis on the steatotic and inflammatory components. This model will enable the in vitro investigation of processes involved in disease progression and the validation of novel molecular targets and RNA-based therapeutic approaches.

miRNA-based therapeutic strategies are emerging as promising approaches for the treatment of liver diseases. Building on results obtained in previous research activities, the group has developed erythrocyte-derived extracellular vesicles (RBC-EVs), engineered to deliver miRNAs and administered in mouse models of MASH and advanced liver fibrosis, with promising preliminary results in terms of efficacy and safety.

Impact

miRNA-based approaches represent an innovative avenue for the development of multi-target therapies capable of simultaneously acting on multiple molecular pathways involved in the disease. This approach holds promise for overcoming the limitations of conventional treatments, which typically focus on a single target, by enabling broader modulation of the pathogenic mechanisms underlying MASH. In this way, the project paves the way for new and more effective therapeutic options for a complex condition that continues to present significant unmet clinical needs.

Pipeline