University of Pittsburgh researchers have identified a new approach to treating liver fibrosis, a condition with limited current treatments. Their findings reveal the enzyme CYP1B1 as a key player in liver scar formation, paving the way for potential new therapies.
Researchers at the University of Pittsburgh School of Pharmacy have made a groundbreaking discovery that could lead to new treatments for liver fibrosis, a condition with limited current options and significant health risks.
Liver fibrosis, characterized by the formation of scar tissue in the liver due to chronic inflammation, can lead to severe complications including cirrhosis and liver cancer. Currently, there are no FDA-approved drugs specifically targeting this condition. Common causes include chronic viral hepatitis, obesity, diabetes and excessive alcohol consumption.
The research, led by senior author Wen Xie, a professor and Joseph Koslow endowed chair of the Department of Pharmaceutical Sciences, along with co-first authors Hung-Chun Tung, a graduate student, and Jong-Won Kim, a postdoctoral fellow, was published in Science Translational Medicine.
For the first time, the study identifies the enzyme CYP1B1 as a critical biomarker and predictor of hepatic stellate cell (HSC) activation, a process that leads to liver fibrosis. HSCs, when activated by liver injury or inflammation, produce excess collagen and other proteins, causing scar tissue formation.
“Inhibition of CYP1B1 led to the accumulation of a sugar called trehalose, which we showed for the first time that trehalose has anti-fibrotic activity,” said Xie in a news release.
The study further demonstrated that treating mice with trehalose, its analog lactotrehalose, or a CYP1B1 inhibitor protected against liver fibrosis.
Significantly, this research highlights a liver function of CYP1B1, an enzyme previously known for its other roles outside the liver. Despite low overall liver concentrations, CYP1B1 is uniquely abundant in HSCs, playing a major part in their activation and the resulting fibrosis.
These findings hold promise for early diagnosis and new treatments for liver fibrosis.
“Our findings are clinically important because we identified CYP1B1 as a predictor of HSC and liver fibrosis in patients, which may help with the early diagnosis of this disease,” added Xie.
Furthermore, the study suggests trehalose and lactotrehalose as potential drugs for liver fibrosis.
Looking ahead, the team plans to conduct comprehensive human studies to validate the role of CYP1B1 in liver fibrosis and assess the therapeutic potential of trehalose and lactotrehalose in human patients.
This breakthrough offers new hope for millions at risk and represents a significant stride in liver disease research, emphasizing the ongoing need for innovative diagnostic tools and treatment options.