Life Insurance for Ebola Scientists

When a German scientist accidentally pricked herself with a needle containing the Ebola-Zaire virus last year, scientists around the world tried to determine what the best course of action would be. Eventually, she agreed to take an experimental Ebola vaccine that had been shown in animals to offer about 50% protection, even when administered after exposure to the virus. And she lived.

But now, scientists say they have something better for such mishaps: a new therapy that, in lab studies, offered complete protection to macaque monkeys when given daily for almost a week after an Ebola injection that would otherwise be fatal. The new treatment, which will be reported online tomorrow in The Lancet, could also be used during Ebola virus outbreaks, the researchers say.

Although Ebola outbreaks are quite rare, the gruesome symptoms—including high fevers, bleeding, and vomiting—and the mortality rate of up to 90% have captured the world's attention and helped propel the virus onto the list of potential bioterror threats.

The lead author of the new study, virologist Thomas Geisbert of the Boston University School of Medicine, who has been working on Ebola for more than 20 years, says that drug development has been slow and difficult. One anticoagulant that Geisbert helped test against the virus was greeted with great enthusiasm when he presented results 7 years ago, because it was the first time a drug had much impact—and yet it only reduced deaths in monkeys by one-third.

For the new study, Geisbert and his colleagues used snippets of so-called small interfering RNAs (siRNA), which can tinker with a virus's replication. These siRNAs are seen as a great promise against viral diseases, but one key problem is that they break down easily inside the body. To prevent this, the team packaged the siRNAs inside so-called stable nucleic acid-lipid particles (SNALPs). Developed by Canadian biotech company Tekmira Pharmaceuticals, these particles are supposed to protect the drugs and help them reach Ebola-infected cells. In a study published in 2006, Geisbert's group had shown that SNALPs containing the siRNA targeting an Ebola protein called polymerase L completely protected Ebola-infected guinea pigs from death.

But primates are much more vulnerable to Ebola, so in the current study, the group added two other siRNAs. They injected the cocktail intravenously in three macaques at 30 minutes after exposure to the virus and then 1, 3, and 5 days later; two of them survived. In a group of four macaques that were given the treatment at 30 minutes and on days one, two, three, four, five, and six after exposure, all survived.

Geisbert says that more work is needed, for instance, to determine the optimal dose and the contribution to the overall effect of each of the three siRNAs. Whether the treatment also works after the animals actually get sick remains to be seen as well; that's hard to test in monkeys because the animals die very soon after becoming infected, he says.

Nonetheless, the study is an important proof of concept, says Heinz Feldmann, an Ebola researcher at the National Institute of Allergy and Infectious Diseases's Rocky Mountain Laboratories in Hamilton, Montana. The new treatment offers the best protection ever seen when given after exposure to the virus, he says.

Feldmann helped developed the vaccine taken by the German researcher. But he says the new treatment will probably be preferable, not just because it is more efficacious but also because, unlike the vaccine, it's not based on a replicating livestock virus. Such vaccines always raise extra safety concerns.

It's important that Geisbert's and other compounds now get tested and developed further, Feldmann says, so that the treatment is on the shelves the next time a researcher or health worker pricks him or herself. "It's been a year since that accident in Germany, and we still don't have anything," he says. "We're in a terrible situation."

The complicated treatment regimen and the fact that treatment has to start soon after exposure may limit the use of Geisbert's compound in the remote areas in Africa where Ebola outbreaks occur. Still, Feldmann, who has worked in several such outbreaks, hopes the therapy might be used there as well. The current strategy is to take care of patients as well as possible and break the chain of transmission by preventing others from getting infected. "As an M.D., I'd like to do something for the individual patient as well," he says.
(Science)