2021/04/27

Inhibition of a mitochondrial protein, a new therapeutic target for cholestatic liver diseases

The presence of this protein slows down the activity of the mitochondria, decreasing their ability to eliminate toxic substances such as certain bile acids.

The research, conducted by CIC bioGUNE and the University Hospital Marqués de Valdecilla-IDIVAL, has been published in the Journal of Hepatology Reports.

(Bilbao, 27 April 2021). Close collaboration between researchers from the Digestive Medicine Unit at the University Hospital Marqués de Valdecilla (HUMV-IDIVAL) and the Liver Diseases Laboratory, led by Prof. Malu Martínez-Chantar, at CIC bioGUNE-CIBER, has once again given rise to a translational research study on cholestatic liver diseases, recently published in the Journal of Hepatology Reports (https://www.jhep-reports.eu/action/showPdf?pii=S2589-5559%2821%2900052-5). The authors report an increase in hepatic levels of a mitochondrial protein, Methylation-Controlled J (MCJ), in patients with chronic liver diseases due to altered bile flow, such as Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). The presence of this protein slows down the activity of the mitochondria, reducing their capacity to eliminate toxic substances such as certain bile acids.

PBC and PSC, although considered rare diseases, are the most prevalent of the chronic cholestatic diseases, and can lead to cirrhosis and liver tumours. These diseases are characterised by damage to the bile ducts leading to the accumulation of bile acids in the liver and, consequently, inflammation and destruction of liver cells.

The study, co-authored by Dr Paula Iruzubieta from HUMV-IDIVAL and Naroa Goikoetxea from CIC bioGUNE, shows that MCJ inhibition by siRNA (small interfering RNA) therapy reduces inflammation and fibrosis formation, which are the main risk factors for the development of liver cirrhosis. The study won the PSC Partners Award at the EASL Liver Congress, one of the most important international congresses in the field of hepatology.

This work represents a new milestone in the collaboration between the two research groups, which had already demonstrated, in previous studies, the importance of the MCJ protein in liver damage caused by hepatotoxic drugs, such as paracetamol, and in steatosis.

These studies reveal that there is a common mechanism of liver damage in different diseases due to the accumulation of toxic substances, and open up a promising new window on the development of treatments to slow the progression of these liver diseases.

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA) and based in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies. CIC bioGUNE has been accredited as a “Severo Ochoa Centre of Excellence”, the highest level of recognition for centres of excellence in Spain.

About the BRTA

The BRTA is an alliance made up of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 12 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Lortek, Neiker, Tecnalia, Tekniker y Vicometch), with the aim of developing advanced technological solutions for Basque companies.
With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three regional provinces, the alliance seeks to promote collaboration among its centres, to strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness, and to spread Basque scientific and technological capacity outside of the Basque Country.

BRTA has a staff of 3,500 professionals, accounts for 22% of the Basque Country’s R&D investment, generates an annual turnover of over EUR 300 million and files 100 European and international patents per year.
CIC bioGUNE, member of the Basque Research & Technology Alliance - BRTA

About the CIBEREHD

The purpose of the CIBER’s (Centre for Network Biomedical Research) thematic area of Hepatic and Digestive Diseases (CIBEREHD), a research centre of the Carlos III Health Institute (Ministry of Science and Innovation) and co-funded by the European Regional Development Fund (ERDF), is to promote and protect health by championing research. This work, the scope of which embraces basic, clinical and translational research, is focused on the field of Hepatic and Digestive Diseases, with the aim of innovating in the prevention of these diseases and furthering progress in the fields of Science and healthcare through the collaboration of benchmark Spanish groups.

About the Biomedical Research Institute Marqués de Valdecilla (IDIVAL)

IDIVAL is the Biomedical Research Institute of Cantabria, accredited by the Carlos III Health Institute, which promotes and develops innovation and health research in the biosanitary field in the region. IDIVAL has 31 health research groups working in the areas of Cancer, Neurosciences, Transplantation, Infection & Immunity and Metabolism, as well as a Cross-Disciplinary area. In the last 5 years, IDIVAL has managed EUR 35 million from external funding obtained by the researchers themselves through competitive projects, agreements and donations.

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