Treating the chronic liver disease

Cecilia Rodrigues

Research Institute for Medicines (iMed), Faculty of Pharmacy, Universidade de Lisboa, Portugal

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one in three people worldwide and is already the most common chronic liver disease globally. It is characterised by an accumulation of liver fat and is linked to obesity, diabetes, atherosclerosis and cancer. Despite efforts over the last decades, only one therapy has recently been approved.

This project focuses on a hitherto little-studied protein, RIPK3 kinase, which has been found to mediate necroptosis, a type of programmed cell death involved in the onset of MASLD. The aim is to develop a new therapy targeting this kinase.

To achieve this, the researchers propose a novel approach that combines an initial phase using computational tools, AI for molecule design, and advanced synthesis; followed by a second phase involving a preclinical evaluation of the safety and efficacy of the treatment in animal models.

The ultimate goal is to obtain definitive proof of concept supporting the therapeutic potential of RIPK3 inhibitors, which will pave the way for future clinical trials in humans.

Testing targeted drug therapy in metabolic liver disease

Stage 2