Despite some recent successes, many viral diseases have no treatment, and most of the existing treatments target a specific virus rather than being able to treat a broad spectrum of viruses. Building on the discovery at Princeton of a family of human proteins that naturally defend against viral infection, a startup company called FORGE Life Science is working to develop broad-spectrum antiviral compounds.
The company is building on research by professors Thomas Shenk and Ileana Cristea demonstrating that proteins known as sirtuins play a role in the body’s natural defenses, or intrinsic immunity, against viruses. With funding from the National Institutes of Health, Shenk, Princeton’s James A. Elkins Jr. Professor in the Life Sciences, and Cristea, professor of molecular biology, found that every member of the sirtuin family showed the ability to inhibit viral replication.
Building upon that basic research, FORGE scientists are looking for small molecules that modulate the activity of sirtuin proteins to fight infection. They are initially targeting select sirtuins, such as 1, 2 and 6, in different combinations to improve the body’s ability to defend against viruses. Because sirtuins inhibit more than one type of virus, a sirtuin-based therapeutic could target multiple viruses.
“Our goal is to treat multiple viruses with one pill,” said Lillian Chiang, FORGE Life Science’s President and CEO. “This could change how we practice medicine.”
Such broad-spectrum capabilities are common in antibacterial medicines, but to date, the few antiviral treatments available are specific for certain viruses. With sirtuin-based treatments, a doctor would not need to identify the virus, which is time-consuming and expensive. Instead, the doctor could prescribe a sirtuin-based drug based on the patient’s symptoms.
Sirtuin-based antivirals also could help treat the opportunistic viruses that infect immunocompromised patients. The antivirals would prevent virus replication even though the immune system is actively suppressed, such as in cases where patients have received organ transplants. Because some FORGE drugs targeting sirtuins can cross the blood-brain barrier, the technology also has the potential to provide treatments for viruses such as rabies and measles. “We can potentially address diseases for which we have no cure,” Chiang said.
Under Chiang’s leadership, FORGE Life Science is conducting preclinical research. The company is located in Doylestown, Pennsylvania. They’ve raised funds from the National Institutes of Health’s Small Business Innovation Research program and from private investors.