Development of a Novel Antifibrosis Drug Candidate
Abstract
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). It is estimated that two billion people worldwide are infected with HBV, making this infection a global health challenge. For some, hepatitis B is a short-term illness, but for others, it can become a long-term, chronic infection. It is estimated that two million Americans are chronically infected with HBV and up to 80,000 will become newly infected each year. Of those with chronic HBV infection, between 15%and 40% will develop progressive liver disease in the form of fibrosis (scarring). Over time, these cases will advance to cirrhosis (late-stage fibrosis), liver failure, and even liver cancer. Antiviral therapy has shown promise for improving the prognosis of hepatitis B; however, these therapies are non-curative and can have serious side effects. Moreover, antivirals are not a treatment option for decompensated cirrhosis, an advanced stage of liver fibrosis. There is therefore a pressing need to develop a therapeutic strategy to reverse liver fibrosis. Such a drug would provide unprecedented hope to both civilian and military patients who have limited options in their battle against HBV. Our lab recently performed a machine learning based drug screen in order to identify compounds that may resolve liver fibrosis. In so doing, we identified OSI-632, a clinical-grade agent that holds potential to block the function of myofibroblasts, the cell type primarily responsible for causing fibrosis in the liver. OS1-632, an oncology drug candidate, has already passed Phase I human clinical trials, thereby proving its safety. As such, this drug offers a path for accelerated clinical development. We propose to repurpose OSI-632 by evaluating its efficacy in HBV-driven liver fibrosis both in vitro and in vivo. Through our research efforts, we will determine whether OSI-632 can resolve HBV-induced liver fibrosis. The successful completion of our proposed study will provide a novel and paradigm changing treatment for chronic liver diseases including hepatitis B.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110136
Entities
People
- Taranjit Gujral
Organizations
- Fred Hutchinson Cancer Center
- United States Army