[Above: The EBNA1 protein (pink) a protein essential for the Epstein-Barr virus (EBV) to survive and replicate.]
The Wistar Institute today announced that it has signed a funding agreement with the Wellcome Trust, a United Kingdom-based charity, to support the development of a new drug to treat cancers associated with Epstein-Barr virus (EBV). The Seeding Drug Discovery Award of up to $4.7 million will support on-going translational research in the laboratory of Wistar Professor Paul M. Lieberman, Ph.D. If successful, the new therapeutic could be the first to treat EBV-related cancer by attacking the virus as it remains dormant in a patient’s cells.
The project is a three-year, multi-stage effort where funding is based on the achievement of defined research milestones, outlined by Lieberman and Troy Messick, Ph.D., a staff scientist in the Lieberman laboratory and co-leader on the project.
“On behalf of The Wistar Institute, I would like to thank the Wellcome Trust for seeing the potential for this project to save countless lives across the globe,” said Russel E. Kaufman, M.D., CEO and president of The Wistar Institute. “This effort reflects translational research at its finest by combining a visionary charitable foundation, a promising line of research, and a solid plan for transforming basic science into practical medicine.”
Epstein-Barr Virus (EBV) is classified by the World Health Organization as a Class I carcinogen, and it is estimated to cause a small but significant portion of all human cancers. The virus may persist in the human body for decades and cause infected cells to become cancerous. It is estimated that EBV causes nearly 400,000 cases of cancer each year, including Burkitt's lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, gastric carcinoma and certain oral and throat cancers.
According to Lieberman, EBNA1, a protein produced by EBV, is a prime target for therapeutic intervention. The protein acts as the master switch that regulates viral gene activity and guides the ability of EBV to remain dormant in the body.
“EBNA1 is expressed consistently in all EBV-related cancer and is essential for the virus to reproduce,” said Lieberman. “Knocking out EBNA1, therefore, could likely eliminate latent Epstein-Barr virus and control the growth of EBV-associated cancer.”
Lieberman heads Wistar’s Center for Chemical Biology and Translational Medicine, a team of researchers whose mission is to develop promising basic research findings into new therapeutics to fight disease, particularly cancer.
To develop an anti-EBV drug, the researchers began a complex screening process to find a small molecule that could chemically bind to EBNA1 and inhibit its ability to function. They began with a library of 600,000 molecular compounds, eventually narrowing the pool down through a series of tests to a handful of leading candidate molecules that have the most potential to serve as the basis of new anti-EBV drug.
With funds from the Wellcome Trust, the Wistar researchers will further optimize their candidate small molecule inhibitors, with the aim of developing at least one chemical compound into a viable drug candidate. This drug candidate could then be used in clinical trials designed to determine its safety and effectiveness for humans.
“This is an investment in drug discovery, enabling a small team of experts to do the type of translational research typically seen in large drug companies,” said Messick. “If successful with the translational research funded by the Wellcome Trust, the program will be in a position to attract a commercial partner to undertake further clinical development.”
Read more in the Philadelphia Business Journal, "Wistar to use grant in fight against Epstein-Barr virus cancers."