Blog Series with the 3RCC, part 9:Unlocking New Therapies: How Cutting-Edge Research Without Animals is Paving the Way for Fatty Liver Disease Treatments!

A research team based in Hubrecht, Netherlands, has developed a new liver organoid model that very closely mimics human livers. This breakthrough offers a promising alternative to animal models and could provide a method for faster, more efficient screening of potential drug treatments.

Nonalcoholic Fatty Liver Disease affects over 25% of the global population, yet there are few effective treatments available. Until now, most research has relied on rodent models, which often fail to accurately mimic human biology. Laboratory-grown human liver cells have also proven unsuitable for large-scale drug testing. However, researchers have now developed a breakthrough organoid model using mini-livers (organoids) grown from human fetal liver cells. These organoids closely replicate real human liver function.

Using advanced genetic tools, the researchers were able to recreate the early stages of nonalcoholic fatty liver disease in these organoids, enabling them to test new drugs. After screening 17 drugs, they identified 5 that reduced fat buildup in liver cells. Notably, genetic differences in the organoids affected how well the drugs worked. They also discovered a gene called FASD2, which could be key in reducing liver fat.

 An advantage of the new organoid model is that it can be grown indefinitely, making it ideal for drug testing. It provides more accurate results than traditional animal models, which often don’t translate well to humans. Additionally, this model aligns with the 3R principle of reducing, refining, and replacing animal testing. The principal researcher, Prof. Hans Clevers, highlighted the significance of this advancement, noting that it offers a more reliable way to discover new treatments and could be expanded to study other diseases. With interest from pharmaceutical companies like Roche, this research could significantly impact drug discovery and safety testing.

Authors: Christopher Cederroth, Jessica Lampe & Robbie I’Anson Price, Swiss 3R Competence Centre

Reference : Hendricks D. et al. (2023) Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis. Nat Biotechnol. 41, pages 1567–1581. https://doi.org/10.1038/s41587-023-01680-4