An experimental type of drug shown to protect rhesus macaques against the Marburg virus could also be tried in the fight to contain the Ebola virus outbreak in West Africa, a scientist says.
The Marburg and Ebola viruses are deadly cousins. Both are filoviruses that cause severe and often fatal hemorrhagic fever and neither has any vaccines or drugs approved for use in humans.
Researchers in Texas and Vancouver-based Tekmira Pharmaceuticals have now shown that giving rhesus macaques an experimental treatment using "small interfering RNA" (siRNA) protected the primates even when treatment began three days after infection with the Angola strain of Marburg virus. Their results are published in Wednesday’s issue of the journal Science Translational Medicine.
The experimental drug technology, siRNA, blocks the recipe the virus uses to make copies of itself, the study’s senior author, Thomas Geisbert of University of Texas Medical Branch in Galveston, told reporters.
In the study, 16 rhesus macaques that received the siRNA treatment survived infection. In contrast, the untreated control subjects succumbed to the disease, the researchers said.
"We demonstrate the ability to completely protect nonhuman primates against the lethal Marburg Angola virus challenge even when treatment is delayed at day three at a time we can detect viremia [presence of a virus in the blood] at the onset of disease showing real-world utility of this technology."
The approach holds promise as a strategy to treat filovirus infection in humans, the journal’s editors said.
'God forbid there was some kind of exposure, I was in an outbreak setting or I had some kind of an incident, I would have no problem taking this product.' - Thomas Geisbert
Another experimental treatment, Mapp Biopharmaceutical’s ZMapp cocktail, works differently. It contains three antibodies that interfere with the ability of the Ebola virus to attach and enter a host cell.
In 2010, Geisbert and his colleagues published a study in The Lancet showing a similar siRNA technology designed to target the Ebola virus also protected rhesus macaques shortly after exposure. The researchers plan to look at whether it also helps in a more real-world scenario of once signs of illness appear.
"We have siRNAs made that work against Ebola virus," Geisbert said. "So it would be possible to take … siRNAs that we already have that are designed against Ebola and have already been used in monkeys against Ebola, for compassionate use during this outbreak."
To do so, a country would need to request the experimental drug from Tekmira.
Whether enough of the drug could be produced quickly enough to help in the current outbreak in West Africa depends on funding and logistics, Geisbert said.
Last week, Tekmira said regulatory issues still have to be worked out before its Ebola product could be used in the outbreak. The company hasn't indicated how much of the experimental Ebola drug it has.
The use of experimental treatments against the Ebola virus also raises safety concerns and thorny ethical questions.
So far, two Americans and three Liberians who’ve received ZMapp are showing signs of recovery. Experts caution it’s impossible to say whether the treatment has aided or hindered recovery. A Spaniard who received the drug died.
During an Ebola outbreak, people generally don't show signs of illness within the 72-hour framework used in the experiments. Geisbert speculated that Day 3 of an infection in a non-human primate might translate to about Day 6 or 7 in a human.
To be licensed as a drug in the U.S., experimental treatments need to pass strict clinical trial standards to check their safety and efficacy. Countries have different requirements for allowing drugs to be tried under conditions of compassionate use.
Geisbert has no problems with the safety issue.
"God forbid there was some kind of exposure, I was in an outbreak setting or I had some kind of an incident, I would have no problem taking this product."
After the World Health Organization’s ethics panel gave the green light to consider using the experimental treatments, it called experts to guide decisions such as who should be considered a priority to receive the limited doses.
Gary Kobinger of the Public Health Agency of Canada in Winnipeg, is an Ebola and Marburg scientist who was not involved in the new study. He called the research "a clear step forward."
But "one has to be careful [basing conclusions on] two animals," he said, referring to the number effectively treated three days after infection.
The research was funded by the U.S. Department of Health and Human Services. Geisbert and three other authors of the study have an intellectual property claim on the use of siRNA technology for filovirus infection.