Research unveils new drug targets for more effective treatment of liver disease
pharmafile | August 22, 2017 | News story | Manufacturing and Production, Research and Development | life sciences, liver, liver cancer, liver disease, pharma, pharmaceuticals
Researchers from KTH The Royal Institute of Technology and Gothenburg University have identified new drug targets in the treatment of liver cancer and fatty liver disease which could be used to create more effective treatments with minimal side-effects.
By utilising analyses of the biological networks generated for 46 human tissues including the liver and combining this with mapped metabolic changes caused by accumulated fat in liver cells, the team was locate liver-specific drug targets which could be inhibited without causing side-effects to other tissues in the body.
This approach utilised data from the Sweden-based Human Protein Atlas project and The Genotype-Tissue Expression (GTEx) project consortia. The computer model predictions were then validated through experiments in human cancer cell lines, mouse liver samples and primary human hepatocytes, finding that inhibiting these targets led to a decrease in cell growth and liver fat content.
These targets include 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).
The findings could lead tomore effective treatments for conditions such as hepatic steatosis, which is caused by excessive fat accumulation in the liver and can lead to cirrhosis, non-alcoholic steatohepatitis (NASH) or even liver cancer. Almost 30% of the adult population us affected, and there are limited options for treatment.
Director of the Human Protein Atlas project and co-author of the research, Mathias Uhlen, commented: “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.”
Matt Fellows
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