Photograph by Lynn Johnson, National Geographic
Published June 9, 2010
Monkeys infected with the deadly Ebola virus have been treated successfully, possibly bringing humans a step closer to a cure.
According to a new study, a team of scientists used special gene-silencing drugs to selectively "knock out" viral proteins in Chinese rhesus macaques infected with a lethal dose of the Zaire Ebola virus. Zaire is the most virulent strain of Ebola—90 percent of infected people die during outbreaks.
(Related: "Where Does Ebola Hide Between Epidemics?")
Ebola spreads via bodily fluids or tainted needles and razors, and it's highly contagious. Infections in humans and other primates typically cause acute fever and headaches, followed by uncontrollable bleeding from the body's openings. Shock from heavy internal and external bleeding usually proves fatal.
Since the virus emerged in central Africa in the late 1970s, people have been searching for ways to prevent or treat Ebola infections. (Take an infectious diseases quiz.)
"Ebola is not only of interest because it can cause high mortality, but also because it can be used as a bioterror weapon," said study leader Thomas Geisbert, a virologist at Boston University.
"There are a lot of groups working on preventive vaccines, but this is the first time someone has developed a post-exposure treatment."
Ebola Virus Blocked From Replicating
Geisbert and colleagues used drugs based on synthetic versions of small interfering RNA, or siRNA, a type of molecule in the body that can interfere with the expression of particular genes. (Get a genetics overview.)
Since genes are the codes the body uses to make proteins, interfering with specific viral genes should stop production of proteins the Ebola virus needs to survive.
"We specifically targeted the L protein, as it kick-starts virus replication," Geisbert said. "If you knock out that protein, you can really inhibit the ability of the virus to replicate."
The team also targeted the VP24 and VP35 proteins, which are involved in disabling an infected host's immune response.
Seven of the nine monkeys in the study received the same amount of the drug over a six-day period. Three of the seven monkeys got the drug every other day, while four received it daily. One monkey in each group served as a control animal and didn't receive the drug.
Analysis of the treated monkeys revealed that, ten days after having been infected with Ebola, the first group of monkeys had very low levels of the virus in their blood. Researchers were unable to detect the virus at all in the group that had received daily doses.
"The siRNAs inhibited the replication of the virus and completely protected the monkeys against death from hemorrhagic fever," Geisbert noted. "This has never been done before."
Ebola Drug Easy to Update
Geisbert thinks the real novelty of the study—published May 29 in the journal The Lancet—is that the scientists were able to deliver the drug to infected cells. That can be a challenge, because synthetic siRNA drugs can activate the body's immune system, triggering inflammation.
To ferry the drug into cells while preventing unwanted side effects, the researchers packed the drug inside fat molecules.
"This capability offers a therapeutic option that has been lacking with certain hemorrhagic fever viruses that have a high level of mortality associated with infections," said Anthony Sanchez, an Ebola researcher at the U.S. Centers for Disease Control and Prevention.
Sanchez was part of a team that successfully tested several Ebola vaccines in nonhuman primates and is now trying to adapt the vaccines for use in humans.
"The interesting part of the technique is that the [siRNA drug] can be quickly synthesized for a specific strain of Ebola virus," Sanchez added. (Related: "New, Fast-Evolving Rabies Virus Found—And Spreading.")
"Thus, if a new strain suddenly appears, whether in Africa or in another region of the world, a therapeutic solution can be quickly generated and deployed for use."
Gaya Amarasinghe, a biochemist at Iowa State University, led the team that determined the chemical structure of the VP35 protein, one of the proteins knocked out in the new Ebola study.
Amarasinghe called the new work "very exciting," because it's possible the siRNA drug and delivery method could be applied to other filoviruses, the class of viruses—including Ebola—that cause severe hemorrhagic fever.
And in a commentary on the study, also published in the Lancet, Heinz Feldmann of the U.S. National Institute of Allergy and Infectious Diseases wrote that the new work is "long overdue and should be considered a milestone in what has been a difficult and frustrating specialty of filovirus research."
Study leader Geisbert believes success in curing Ebola in nonhuman primates could translate into a human model for treatment. But the question of human clinical trials for an Ebola drug boils down to funding.
"The technology is pretty much ready to go," Geisbert said. But "the small global market for this drug is not much of a financial incentive for drug companies to pursue a vaccine. Investors aren't going to do that—it has to be the government."
Amarasinghe agrees, and he also points to the rising cost of doing research with high-priority pathogens. That's because, inflation aside, researchers need highly secure—and thus expensive—biocontainment facilities to study these deadly diseases.
"Under the FDA's 'animal rule,' potential drugs that perform well in animal-efficacy studies can be substituted for human clinical trials, as long as appropriate human safety studies have been conducted," he explained.
"Ebola can qualify under that rule, and if promising candidates [for drugs] are identified, at the very least, mechanisms are in place to move them forward into the product-development phase."
The new Ebola drug study included scientific collaboration with Tekmira Pharmaceuticals and the United States Army Medical Research Institute of Infectious Diseases.
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