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.”