Researchers in Sweden have identified a number of drug targets that can be used in the development of new efficient treatment strategies for fatty liver disease and liver cancer with minimum side effects.

KTH the Royal Institute of Technology’s Science for Life Laboratory (SciLifeLab) research centre and Gothenburg University employed the biological networks generated for 46 major human tissues in order to identify the liver-specific gene targets.

The researchers mapped the metabolic changes caused by accumulated fat in liver cells, and combined this data with an analysis of biological networks of liver and other human tissues.

Doing so enabled them to identify the liver-specific drug targets whose inhibition will not cause any side effect to other human tissues, said lead author Adil Mardinoglu.

Mardinoglu added that the team’s network modelling approach, which relied on data from the Sweden-based Human Protein Atlas project and The Genotype-Tissue Expression (GTEx) project consortia, can be used in the identification of drug targets and eventually in the development of efficient strategies for treating a number of chronic liver diseases.

The researchers identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell, (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3) and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

Mathias Uhlen, director of the Human Protein Atlas project and co-author of the paper, said: “I am extremely pleased that the resource created through the Human Protein Atlas effort has been used in the analysis of clinical data obtained from liver disease patients and that this analysis has led to the identification of liver-specific drug targets that can be used for treatment of this clinically important patient group.”

The research has been published in Molecular Systems Biology, an EMBO press journal.

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