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Ebola Treatment Shows Promise in Monkey Study
Antiviral drug cured animals with advanced infections, researchers say
By Dennis Thompson
WEDNESDAY, April 22, 2015 (HealthDay News) -- An experimental drug being tested on Ebola victims in Sierra Leone has proven effective in treating infected monkeys during laboratory trials, a new study reports.
The antiviral drug, TKM-Ebola, cured three monkeys infected with Ebola, said study senior author Thomas Geisbert, a professor of microbiology and immunology at the University of Texas Medical Branch at Galveston.
The treatment is the first that has been demonstrated in the lab to be effective against the Makona strain of Ebola, which is responsible for the ongoing epidemic in West Africa, researchers reported April 22 in the journal Nature.
TKM-Ebola works by targeting the genetics of Ebola. It uses molecules called small interfering RNA -- also known as siRNA or "silencer" RNA -- to disrupt the delivery of genetic blueprints that the virus uses to replicate.
One of the benefits of the drug is that its "silencer" RNA can be quickly modified to target specific viral strains -- in this case, the Makona strain of Ebola, the researchers explained.
"The drug is rapidly adaptable. We wanted to show it works against this outbreak strain, and we've done that," Geisbert said. Researchers used data gathered from the complete genetic sequencing of the new Ebola strain to target the drug specifically against that strain.
The West African outbreak of Ebola, which occurred mainly in the nations of Guinea, Liberia and Sierra Leone, has caused 10,730 deaths, according to the U.S. Centers for Disease Control and Prevention. More than 25,890 suspected Ebola infections have taken place during the outbreak.
The Wellcome Trust began phase II clinical trials in March on this version of TKM-Ebola, providing the drug to Ebola patients in Sierra Leone. Results of the trial, which will assess safety and effectiveness, are expected later this year.
In the new lab study, researchers administered TKM-Ebola to a trio of monkeys three days after their exposure to Ebola. Three other monkeys also were infected but not treated.
Although all of the monkeys showed evidence of advanced Ebola infection, those receiving treatment had milder symptoms and recovered fully, the researchers said. The untreated monkeys succumbed to the disease on days eight and nine, similar to the time frame that has been observed in actual patients, Geisbert said.
TKM-Ebola also protected against liver and kidney damage, and blood disorders that occur during an Ebola infection, and effectively reduced the amount of virus in the monkeys' bodies, the researchers said. The drug also appeared to stimulate the treated monkeys' immune system.
"Not only did the treated ones survive, but they had an antibody response which suggests it will have a lasting effect," said Dr. Lee Norman, an Ebola expert and chief medical officer of the University of Kansas Hospital.
Dr. Amesh Adalja, a senior associate at the UPMC Center for Health Security in Baltimore, called TKM-Ebola a "remarkable drug" because of the way it works and its adaptability.
"Since this drug platform is highly adaptable, the researchers were able to modify the product to be completely targeted at the unique West African outbreak strain, showing the resiliency of the siRNA approach to mutations," Adalja said. "These data support the prior and future experimental use of TKM-Ebola for human disease, as an important tool in controlling future outbreaks of this disease."
Future lab studies will focus on how late in Ebola infection the drug can be administered and still be effective, Geisbert said.
"The natural logical next step is to find out how far we can push it out," he said. "There's going to be a point where no drug on Earth is going to be able to protect that animal's life."
Researchers also plan to investigate whether a lower dose of the drug will still be effective, Geisbert said, and also eagerly await the results of the Sierra Leone human trial.
Researchers from the drug's manufacturer, Tekmira Pharmaceuticals Corp., of British Columbia, Canada, also participated in the study, which was partially funded by the U.S. National Institutes of Health.
For more on Ebola, visit the U.S. Centers for Disease Control and Prevention.
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