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STRATEGY TO INHIBIT TGF-Beta IN LIVER DISEASE

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Novel treatments against chronic liver diseases

Chronic liver diseases (CLD) are the leading causes of morbidity and mortality worldwide with enormous socio-economic costs. Research into the molecular mechanisms that cause these diseases will help in the design of effective treatments.

Fundamental Research
Health

CLDs and their end-stages – cirrhosis and hepatocellular carcinoma (HCC) –are caused by chronic hepatitis C (HCV) and B (HBV) virus infections, alcohol abuse and non-alcoholic steatohepatitis (NASH) as a result of metabolic syndrome. Liver transplantation is currently the only available therapy for terminal liver failure, which is however associated with many complications. It is well recognised that the cytokine transforming growth factor (TGF)-beta plays a pivotal role in the sequence of events leading to end-stage CLD. However, the complexity of the underlying aberrant responses in the cells and the organ associated with CLD and HCC is poorly understood. The EU-funded IT-LIVER project brought together a broad spectrum of scientific and technological expertise to discover drugs and treatment modalities for CLD and HCC. The established European Network focused on integrating efforts and resources to provide a comprehensive research and training programme for a total of 15 new researchers. Research training included technologies of basic molecular and cell biology, drug discovery and delivery systems, as well as development of preclinical models and preclinical treatment modalities. During IT-LIVER, the fellows studied the molecular mechanisms underlying intracellular signalling of the TGF-beta family of regulatory peptides and its relevance in liver pathologies. Using a plethora of innovative technologies such as omics analyses, scientists underscored the relevance of the TGF-beta pathway in liver fibrosis and HCC formation. This is expected to serve as the basis for the design of targeted therapeutic tools in both in vitro and in vivo models. In addition, several new strategies were tested for inhibiting TGF-beta signalling, while the discovery of TGF-beta related biomarkers will help identify patients most likely to benefit from TGF-beta inhibition. Considering the lack of efficient therapeutic tools for CLD, the findings of the IT-LIVER project advance existing knowledge and have important socioeconomic implications.

Keywords

Chronic liver diseases, hepatocellular carcinoma, TGF-beta, IT-LIVER, biomarker

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