UCSD discovery could lead to liver disease breakthrough

SAN DIEGO — UC San Diego researchers Thursday announced the discovery of an enzyme that, if inhibited, could help prevent a chronic and aggressive liver disease.

The enzyme, caspase-2, is critical to the development of non-alcoholic steatohepatitis, an aggressive form of non-alcoholic fatty liver disease. While the exact cause of NASH is unknown, researchers believe one factor leading to NASH is a high amount of stress on the endoplasmic reticulum, causing a buildup of cholesterol and triglycerides.

Researchers found in studies of both mice and human liver specimens that caspase-2 is responsible for major aspects of the disease like lipid accumulation and liver inflammation. By inhibiting the gene in mice that produces caspase-2, Dr. Michael Karin and his team determined just how large of a role the enzyme plays in the development of NASH.

“Our results show that caspase-2 is a critical mediator of NASH pathogenesis, not only in mice but probably in humans as well,” Karin said. “While explaining how NASH is initiated, our findings also offer a simple and effective way to treat or prevent this devastating disease.”

Researchers also discovered that increased caspase-2 helps over- stimulate a protein reaction that leads to an accumulation of lipids in the liver, leading to liver disease. Karin and his team hope to eventually develop their findings into a caspase-2-restraining drug of some kind and ultimately a treatment option.

“This study was a great step forward in being able to understand the causes, and explore possible new treatments for patients with NASH and [liver disease],” said co-author Dr. Rohit Loomba. “It is our hope to eventually translate and validate these study results using a much larger cohort of human subjects.”

Notice: you are using an outdated browser. Microsoft does not recommend using IE as your default browser. Some features on this website, like video and images, might not work properly. For the best experience, please upgrade your browser.