• Tuesday, August 27, 2019 @ 12:00 am

3D InSight human liver models helped assess efficacy of praliciguat, a systemic small molecule sGC stimulator, in reducing hallmark symptoms of fatty liver disease.

InSphero today announced that in a recent study published in the Proceedings of the National Academy of Sciences (PNAS), researchers at Cyclerion Therapeutics, a clinical stage biopharmaceutical company, used InSphero 3D InSight Human Liver Disease Microtissue models to evaluate praliciguat, a systemic small molecule stimulator of soluble guanylate cyclase (sGC), as a potential treatment for non-alcoholic steatohepatitis (NASH) and fibrotic liver disease. Study results support further investigation of sGC stimulation as a potential therapeutic approach for NASH and fibrosis, and validate the utility of 3D InSight human liver disease models for preclinical drug screening.

sGC is a complex of two proteins found in tissues throughout the body. It mediates nitric oxide signaling and the cyclic guanosine monophosphate (cGMP) pathway known to regulate diverse and critical biological functions, including inflammatory and fibrotic processes. The Cyclerion research team discovers and develops systemic and tissue-targeted sGC stimulators, intended to maximize the desired effects for the target disease, while minimizing side effects.

“The results published in this paper provide important validation of the sGC stimulator mechanism as a potential treatment for NASH and fibrotic liver disease. We expect to apply these learnings to our ongoing late-stage discovery program focused on a tissue-targeted sGC stimulator designed to maximize this pharmacology in the liver,“ said Cyclerion Chief Scientific Officer Mark Currie. “Our collaboration with InSphero provided further exciting insights into the effects of praliciguat on hepatic cells, and their 3D human liver microtissue models enabled us to better understand how these results may translate to clinical settings.“

InSphero partners with pharmaceutical companies to provide comprehensive solutions and disease models for investigators engaged in non-alcoholic fatty liver disease (NAFLD) research and drug development. The 3D InSigh Human Liver Disease Model used in this study includes a phenotypically relevant microtissue co-culture of primary human hepatocytes, Kupffer cells, hepatic stellate cells, and liver endothelial cells, with specially formulated media and inducers to stimulate inflammation and scarring of the liver (fibrosis). This 3D InSight Human Liver Disease Platform is ideal for high-throughput and longitudinal studies of NAFLD and NASH.

“Our research partnership with Cyclerion exemplifies how we support truly innovative pharmaceutical research with our versatile portfolio of scalable drug discovery and safety platforms. Our discovery platforms accelerate pharmaceutical R&D substantially, as we were able to show here,” said InSphero CEO and Co-founder, Dr. Jan Lichtenberg.

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