Researchers at Memorial Sloan Kettering Cancer Center (MSK), The Rockefeller University, and Harvard Medical School have made an important discovery about the hepatitis B virus (HBV) that could lead to a new treatment for chronic infections. Their findings were published in the journal Cell.
The team identified a potential therapeutic target: If one could disrupt the formation of chromatin structures on HBV DNA, then one could disrupt the virus’s ability to start and maintain an infection. They tested five small-molecule compounds known to impair chromatin formation. Only one blocked the production of protein X in liver cells: an anticancer drug candidate called CBL137.
“This discovery opens the door to understanding how the X gene is regulated and how HBV infection is established,” said Dr. David, a professor at MSK who led the study. “Moreover, we were elated to discover a potential therapeutic opportunity: If one could disrupt the formation of these chromatin structures, then one could disrupt the virus’s ability to start and maintain an infection.”
CBL137 worked at very low concentrations – many times smaller than participants in clinical trials for cancer were receiving, and using doses that only affected the virus, but not human cells. “This made us very optimistic about the possibility of developing a treatment approach while preventing or limiting side effects,” Dr. David said.
Next steps for the research include studying the safety and effectiveness of CBL137 in animal models – though these are limited due to the narrow range of species HBV can infect, the researchers say.
“Without the contributions from all the labs, this research would not have been possible,” Dr. Prescott said. “When it came time to find a place to do my postdoc, I was like, ‘Why would I ever leave?'”
