Researchers have discovered novel candidate drug targets for non-alcoholic fatty liver disease (NAFLD) by utilizing the most recent technologies, including single-nuclear sequencing of mouse and human liver tissue and advanced 3D glass imaging of mice to characterize important scar-producing liver cells.

These cutting-edge techniques allowed the researchers to identify a network of cell-to-cell communication that drives scarring as liver diseases progresses. The study was published in Science Translational Medicine, and might help to pave a way to new therapies. Single-nuclear sequencing was done in performed on human liver tissue from 9 Nonalcoholic steatohepatitis (NASH) patients and two controls, as well as mice models of NASH. They identified 68 pairs of putative drug targets that were shared by the two species.

The researchers found that stellate cells create a dense network, or meshwork, of contacts among themselves in advanced disease that facilitates the 68 novel interaction pairs which were not yet described in this condition. They confirmed the significance of one such pair of proteins, NTF3-NTRK3, by using a previously developed drug molecule to disrupt NTRK3 in human tumours and repurposed it to establish its potential as a new therapy to treat NASH fibrosis.

The researchers postulate that some medications may be more successful earlier than others at more advanced stages of the disease because the circuitry of how cells communicate with one another changes as the disease progresses. Hence, the same medication might not be effective at all illness stages.

The researchers are presently optimizing the NTRK3 inhibitors to treat liver fibrosis. They further intend to functionally evaluate all possible interactors in a cell-culture system before considering them in preclinical liver disease models and also study if the fibrosis of other organs, such as the heart, lungs, and kidneys, is caused by interactions between fibrogenic cells that are comparable.

(Source: https://theprint.in/health/research-potential-new-targets-identified-in-non-alcoholic-fatty-liver-disease/1298667/)