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Scientists feel urgency trying to find Ebola cure

Mon., Aug. 4, 2014

SEATTLE – Scientists working on an Ebola cure say the growing outbreak in West Africa lends urgency to their mission.

“To see how fast it’s spreading is incredible,” said University of Washington immunologist Michael Gale Jr. “It shows how dire the need is for antiviral therapy.”

Gale and colleagues at Kineta, a Seattle biotech company, have identified compounds that stop the spread of Ebola and other viruses in laboratory experiments on human cells.

Another Seattle lab, headed by UW microbiologist Michael Katze, is using genetic analysis to understand how some individuals survive the deadly infection and to screen existing drugs for Ebola-fighting ability.

Katze and his team have also helped analyze the body’s response to an experimental Ebola vaccine that proved highly effective in monkeys.

Neither Seattle lab is close to bringing a drug to market, but researchers say the outlook is promising – at least from a scientific perspective.

The biggest hurdles are likely to be economic.

Despite the deaths of more than 700 people in recent weeks, Ebola remains a very rare disease, concentrated in some of the world’s poorest countries, Gale pointed out.

“There’s no money in it,” he said. “American pharmaceutical companies won’t touch anything unless there’s at least a billion-dollar market potential.”

Gale hopes to avoid that pitfall by developing treatments that are effective against a wide array of viruses in addition to Ebola – including flu, West Nile virus, dengue fever and possibly the common cold.

His team is sharing in a five-year, $8.1 million federal grant to identify compounds that rev up the natural infection-fighting ability of cells, allowing them to repel many types of viruses.

In earlier work, Gale identified an enzyme that is key to activating what’s called the innate immune system – the body’s first-line defense against outside invaders.

The enzyme “turns on literally hundreds of genes that fight off viral infection,” he said.

Some viruses, like Ebola, have devised ways to dial down that enzyme, said Shawn Iadonato, chief scientific officer for Kineta.

At the company’s South Lake Union lab, workers screened more than 100,000 chemical compounds for the ability to dial the enzyme up. They identified 20 promising candidates, three of which stood out in follow-up tests.

No labs in Seattle are equipped or approved to work with Ebola virus, so those tests are conducted at a University of Texas facility in Galveston. “There’s a special building with 3-foot-thick concrete walls, negative pressure, Pine-Sol showers, all that kind of stuff,” Gale said. Researchers who handle the virus wear respirators and full protective gear.

The next step in the project is to see if the compounds work as well in monkeys as they do in test tubes, Gale said.

The difficulty of conducting human tests with a disease as deadly as Ebola has stalled progress on other promising treatments, including vaccines, said Angela Rasmussen, a UW researcher who works with Katze.

She and her colleagues have developed strains of laboratory mice that mimic human populations in terms of their genetic variability. When the mice are infected with Ebola in experiments at the federal Rocky Mountain Laboratories in Montana, the animals exhibit the same range of symptoms as infected people, including hemorrhage and liver failure.

Most of the mice die. But about 20 percent get sick, lose weight and then recover.

“That’s what we see in human outbreaks,” Rasmussen said. “Some people can survive, perhaps because they have some genetic trait or immunity.”

By analyzing the mouse genetics in detail and comparing it with the animals’ symptoms and outcomes, the scientists hope to figure out what allows some individuals to recover.

They’re also screening drugs already on the market, to see if they might prove useful.

Though the prospects are good that treatments can be developed, not many U.S. labs are focused on Ebola, Iadonato said. Only a few are working on broad-spectrum antivirals.

Much of the funding comes under the umbrella of biodefense, out of concern that the Ebola virus could be used as a weapon.

Considering the number of cases this year, the National Institutes of Health decided to fast-track initial human trials on a promising vaccine that worked well in monkeys. But even if the vaccine proves safe and effective, approval wouldn’t come in time to help stem the current outbreak.

Rasmussen, who has assisted in studies on another promising vaccine, would like to see the process accelerated even more.

“This is an emergency situation where people’s lives are at stake,” she said. “It’s a terrible human cost, and it’s a terrible way to die.”


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