Researchers from the Marqués de Valdecilla University Hospital and the Marqués Valdecilla Research Institute Foundation (IDIVAL) have collaborated in a study studying the GalNAC-MCJ molecule as a promising therapeutic agent for patients with fatty liver and advanced stages of disease. This international project is led by CIC bioGUNE Liver Disease by Dr. Malu Martínez Chantar and is the result of a close collaboration that the Valdecilla Hospital Digestive service has been carrying out with the CIC Biogune.
The work, which has recently been published in the journal Communications Nature Communications ’, has carried out preclinical studies in fatty liver toxicity models with GalNAC molecules, designed by Alnylam Pharmaceuticals, targeting the mitochondrial respiratory chain inhibitor MCJ.
"Mitochondria is the main energy organelle of our cell and is essential for actively metabolizing lipid accumulation that induces a toxic response associated with this liver pathology," explained Dr. Malu Martínez Chantar.
"Therefore, the mitochondria is one of the first defense barriers of our liver and loses its activity in advanced stages of the disease," he concluded.
Liver fat deposition disease (EHDG) is one of the main lines of research of the Clinical and Translational Research Group Group on Digestive Diseases led by Dr. Javier Crespo and the Marqués de Valdecilla University Hospital.
In fact, in Valdecilla different studies have been carried out on this disease, since in Cantabria around 24% of Cantabrians suffer steatosis or fatty liver, a percentage "very similar" to that of other autonomous communities in Spain and, in general, to that of the western world.
It is estimated that around 1,500 million people suffer from fatty liver. This abnormal accumulation of lipids in the liver tissue produces an inflammatory response and a subsequent induction of collagen by the so-called star cells, which can eventually lead to the development of fibrosis and severe liver dysfunction.
15% of patients with mild liver disease progress to more advanced stages of the disease and with increasing severity, such as fibrosis, cirrhosis and, finally, liver cancer, in a percentage close to 10%. In fact, epidemiological data suggests that the incidence of liver cancer derived from fatty liver has increased significantly compared to other historically prevalent etiologies such as viral hepatitis.
The research has been carried out by the CIC bioGUNE Liver Disease laboratory, led by Dr. Malu Martínez Chantar, researcher at CIC bioGUNE and the CIBER of Liver and Digestive Diseases (CIBERHD), in collaboration with Dr. Mercedes Rincón, from the University of Colorado (Anschutz Medical Campus of Medicine), and Dr. Juan Anguita (CIC bioGUNE), within a consortium of national and international scientists, both from hospitals and from basic and translational research centers, such as: the Marqués University Hospital de Valdecilla (Santander), Geisel School of Medicine in Dartmouth (United States), Department of Physiology of the Faculty of Medicine and Nursing of the University of the Basque Country (UPV / EHU), Institute of Health Research Biocruces, Institute of Health Research of The Princess and University of Colorado (United States).
Ref. Nat Communactions. 2020 Jul 3;11(1):3360. doi: 10.1038/s41467-020-16991-2. Silencing Hepatic MCJ Attenuates Non-Alcoholic Fatty Liver Disease (NAFLD) by Increasing Mitochondrial Fatty Acid Oxidation. Lucía Barbier-Torres, Karen A Fortner, Paula Iruzubieta, Teresa C Delgado, Emily Giddings, Youdinghuan Chen, Devin Champagne, David Fernández-Ramos, Daniela Mestre, Beatriz Gomez-Santos, Marta Varela-Rey, Virginia Gutiérrez de Juan, Pablo Fernández-Tussy, Imanol Zubiete-Franco, Carmelo García-Monzón, Águeda González-Rodríguez, Dhaval Oza, Felipe Valença-Pereira, Qian Fang, Javier Crespo, Patricia Aspichueta, Frederic Tremblay, Brock C Christensen, Juan Anguita, María Luz Martínez-Chantar, Mercedes Rincón. PMID: 32620763 DOI: 10.1038/s41467-020-16991-2
