The UW searches for Ebola cure

Angela Rasmussen examines cells of an animal sample

Since its most recent outbreak in February, Ebola virus disease has infected a total of 2,240 and killed 1,229 people, as of Aug. 19, 2014. Having sent two infected American missionaries and a Spanish priest back to their respective countries for treatment, the outbreak has become a global emergency.

As the World Health Organization urges for an internationally-coordinated response to stop and reverse the spread of the virus, UW scientists are researching a cure for Ebola.

The Katze Lab, a research lab of the UW Department of Microbiology lead by Michael Katze, is doing basic research with the aim of drug or vaccine development.

“We’re making … progress in developing a good mouse model that mimics human disease, which is a good first step towards testing drugs and vaccines,” Katze said.

The lab is using genetic analysis to understand which genes can fight off the virus better than other genes, based on a panel of genetically-diverse mice representing the human population.

Until now, all mice at the lab died when given the Ebola virus. But in the new panel of genetically-diverse mice, some die, some develop hemorrhagic disease, and some survive; it’s more like what would occur in an actual pool of human patients.

Some people are more genetically equipped to fight off Ebola than others, and Katze is trying to figure out which genes enable these people.

The sensationalized, graphic hot-zone description of Ebola has developed the common misconception that everybody is liquefying and vomiting up their stomach lines. But Angela Rasmussen, the project manager of the Katze Lab, stresses that people react to the virus differently, as the hemorrhagic syndrome only manifests in about 30 to 50 percent of the human patients.

What many tend to forget is that Ebola is a virus, like the flu.

“You and I could get the same dose of the same strain of flu at the same time and I get really sick while you just have a mild cold. This kind of thing happens all the time,” Rasmussen said.

Unlike the patients in West Africa, whose medical histories are in question or non-existent, the carefully arranged panel of mice ensures that the host response is genetic.

“We know where the mice are from and what they’ve been exposed to, so when a mouse in the lab survives, we know that there’s something genetic that allows them to fight off Ebola,” Rasmussen said.

Katze is working to improve the survival numbers of the genetically-diverse pool of mice when given a drug. The lab studies genes that the host expresses or shuts off in response to Ebola infection via DNA sequencing. It also compares the gene profile to other diseases that can be treated by existing FDA-approved drugs. Its ultimate hope is to find or develop drugs that enhance the genes that help fight off Ebola.

Unrelated to Katze, another research for Ebola cure is in progress at Kineta, a Seattle biotech company. Kineta works with UW immunologist Michael Gale Jr. and his colleagues to identify broad-spectrum antiviral compounds that activate certain critical components of the immune response in human.

“What’s important about the work [Kineta] is doing is that there isn’t any broad-spectrum antiviral product that has been approved for use,” Shawn Iadonato, executive vice president and chief scientific officer at Kineta, said.

There are broad-spectrum antibiotics that work against various bacteria, but vaccines are only targeted for a specific virus. Hence, many viruses lack adequate drugs for treatment. Broad-spectrum antiviral compounds that Kineta seeks to identify are to be effective against a wide range of viruses in addition to Ebola, including dengue fever, flu, and the common cold. Though progressive and successful so far, both lab experiments are not coming up with drugs anytime soon.

“It’s hard to know how close we are to actually testing drugs and vaccines, and the process by which you get something like that approved by the Food and Drug Administration (FDA) is a lengthy process,” Katze said.Rasmussen’s stance on the progress is more hopeful. “I can’t give a set time frame, but probably within the next year, you’re going to see a lot more activities of taking things from pre-clinical development into clinical trials in humans, especially vaccines,” Rasmussen said.

Kineta’s prospect aims for an even longer period. “We are optimizing promising candidates, which can enter clinical development in five years and be evaluated in clinical trials in five to seven years,” Iadonato said.

Until now, the FDA has been reluctant to approve human trials because the Ebola outbreaks have been sporadic and small-scale.

Although the recent outbreak already killed nearly 1,000, Katze stresses that the relative urgency of the virus needs to be put in perspective, as the flu kills 30,000 in the United States alone. “But Ebola is a lot sexier than flu at the moment with the hot-zone, the outbreak, and the contagion. It’s more dramatic, which makes it more fun for the media and for scientists,” Katze said.

Hence, the National Institute of Allergy and Infectious Diseases is going to test vaccines in September of 2014. “The recent Ebola outbreak has really spurred renewed interest in pursuing the kind of work that needs to be done to get something, even experimentally, on the market that you can offer people,” Rasmussen said.

Reach contributing writer Jessica Kim at Twitter: @jekkimes

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