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Back to research topics Biotherapy

Non-alcoholic steatohepatitis (NASH) is a multifactorial chronic liver disease of increasing prevalence worldwide, leading progressively to hepatic fibrosis, which can result in cirrhosis or hepatocellular carcinoma. None of the current anti-fibrosis treatments appear to be very convincing in clinical trials. It is therefore necessary to propose new therapeutic strategies, and the use of small interfering RNAs is of major interest in this context.

Histological sections of murine liver showing steatosis (Hematoxilin/Eosin stain) and fibrosis (Sirius red stain)

Within the team, we have set up a metabolic model of liver fibrosis, induced by a specific diet deficient in essential amino acids. The interest of this model is that the establishment of fibrosis more closely follows the evolution of a metabolic disease observed in human NASH, with induction of steatohepatitis and fibrosis. In this model, siRNA-based therapeutic strategies will be implemented by adapting existing self-assembling nanoparticle vectors to make them more effective, less toxic and more specific to targeted liver cells, in particular hepatic stellate cells. The monitoring of fibrosis markers will be an essential part of this project to assess the efficacy of the therapeutic strategy.

In addition to conventional monitoring, other methods are envisaged, such as morphological characterization of collagen fibers on liver sections using multiphoton imaging (collaboration with the Institut Pasteur imaging department) or non-invasive imaging of liver fibrosis using magnetic resonance elastography (collaboration with CNRS-CREATIS UMR5220, Lyon). This project, funded by an ANR young researcher grant, is coordinated by Céline HOFFMANN.

Read the article in Scientific Reports

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