The Ebola outbreak in West Africa continues to take a major, deadly toll: according to the World Health Organization, deaths now exceed 10,000, and more than 24,000 people are infected.
“Part of the reason people get so sick is that Ebola shuts down innate immune response, so people have no defense of their own against the virus,” says Michael J. Gale, Jr., Ph.D. Gale (pictured, far right), who leads UW Medicine’s Center on Innate Immunity and Immune Disease, is part of a consortium — including Kineta Pharmaceuticals and the University of Texas Medical Branch at Galveston — that thinks the immune system will hold a key to fighting Ebola.
The key to immune response, in this case, is RIG-I. It’s a protein that can recognize viral nucleic acid and spur a cell to fight off viruses. Unfortunately, it doesn’t always work. “The Ebola virus does a really good job of inhibiting RIG-I,” says Gale.
In response, Gale and his collaborators are working on strengthening RIG-I so that it can respond to Ebola. As Ebola curtails RIG-I’s activity, the researchers work around it, using small molecules to activate the protein. “We come in on the other side of the blockade, and we turn everything on,” Gale says. “The cell goes to work and starts expressing genes with antiviral action to shut down the virus.”
David La, Ph.D., is a senior research fellow with the Institute for Protein Design (IPD) at the University of Washington, and he and his colleagues are also researching Ebola. La started to work on the project about three years ago, when very little was known about the condition.
“I wanted to work on a problem that was going to be useful to many people if it were solved,” he says.
At the IPD, researchers create proteins to interfere in the process of disease. “We computationally design new protein molecules to be used as highly effective therapeutics for blocking the fusion and entry of the Ebola virus into human cells,” says La.
Collaborating with the Scripps Research Institute, Vanderbilt University, the Albert Einstein College of Medicine and the U.S. Army, La and his colleagues are looking for both a medication and a diagnostic. Current diagnosis of Ebola involves RNA sequencing, a process that can take a day or two — a long time for uncertainty when dealing with a deadly disease and a public health risk.
“We would like to diagnose whether you have the virus or not within a half-hour or so,” La says.
Both La and Gale are pleased with their progress. La’s collaborators are testing several designed proteins to see if they neutralize the virus; he hopes they’ll move to the next, crucial phase of testing this year. Gale is in a similar place in the pathway to drug development.
“We can get a 99.9 percent drop in the virus [in a culture dish],” Gale says. If the next step goes well, he and his colleagues may get permission to test the drug in humans on an accelerated schedule.
Two labs, two approaches, one motivation: saving lives. “An outbreak happens almost every year,” says La. “So we’re trying to prepare.”