Stanford’s new Center of Excellence for Translation Research will focus on ushering potential antiviral therapies from bench to bedside.
“As a physician-scientist, there is nothing more exciting and motivating than to translate basic science discoveries in my laboratory into potential new therapies for my patients here and around the world,” said Jeffrey Glenn, MD, PhD, associate professor of gastroenterology and hepatology and of microbiology and immunology.
Glenn led the creation of the center, which opened in April, after receiving a five-year, $28 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Traditional research follows a “one drug, one bug” model in which scientists attempt to find a drug that interferes with one function within a particular virus, said Glenn. But viruses replicate and evolve so quickly that they can rapidly become resistant to the drug, rendering it useless.
“The idea of the center is to change that paradigm for antiviral therapy,” said Glenn. Instead of finding drugs that target the virus, the center aims to develop new therapies that block resources in the host cell that the virus needs to copy itself. Host cells often have a backup pathway they can use when another is blocked. Viruses, which rely on human cells to provide the machinery and raw materials they need to replicate, may not be able to capitalize on the backup pathways. Because the genes encoding these building blocks are not under the virus’ control, it may be harder for the virus to evolve resistance. This new type of therapy could be effective against several types of viruses — “one drug, multiple bugs.”
One such possible drug, which Glenn identified as a graduate student, stops hepatitis D, a deadly liver virus, from using a cellular building block. The drug is now in phase-2 clinical trials at the NIH and in Turkey, where hepatitis D is endemic. In the future, Glenn hopes to test it on other viruses.
The center includes several core facilities to support its work, including a pharmacology core facility encompassing a group of experts and specialized lab equipment that has the capacity to track the metabolism and movement of drugs through the body, and which houses animal models, including mice with humanized livers, to enable prediction of human-specific effects. The center also contains a medicinal chemistry core run by Stanford ChEM-H for synthesizing new drugs, and a core that will provide regulatory expertise and guidance to help ensure that interesting findings in the lab are translated into real products that can be tested in clinical trials.
Besides Glenn, there are 11 Stanford faculty members within the center: Jan Carette, PhD; Mark Kay, MD, PhD; Vijay Pande, PhD; Karla Kirkegaard, PhD; Chaitan Khosla, PhD; Chris Garcia, PhD; Shirit Einav, MD; Purvesh Khatri, PhD; Gary Peltz, MD, PhD; Daria Mochly-Rosen, PhD; and Kevin Grimes, MD. Kevan Shokat, PhD, of UC-San Francisco is also a member.
Within Stanford the researchers will collaborate with organizations including ChEM-H, SPARK and theInstitute for Immunity, Transplantation and Infection. The scientific advisory committee is composed of faculty from Stanford and other universities, members of the Gates Foundation and pharmaceutical company scientists.
As pharmaceutical companies conduct increasingly fewer studies into early drug discovery, Glenn said the center can help meet the demand for antiviral therapies.
“We’ve never had greater tools at our disposal,” he said. “This is really the golden age of developing new therapies — what is lacking is sufficient resources to maximize these efforts — and this center can now be leveraged to help change the model for early drug development.”