Drug for Ebola-Like Virus Shows Promise in Monkeys
WEDNESDAY, Aug. 20, 2014 -- A new experimental drug has saved a group of rhesus monkeys from deadly Marburg virus, a very close cousin of Ebola virus that kills up to 90 percent of those it infects, researchers report.
The drug protected 16 monkeys infected with lethal doses of Marburg virus, even when it was given three days after infection, according to a study published Aug. 20 in the journal Science Translational Medicine.
This is the first drug ever shown to completely protect monkeys after they have been exposed to Marburg-Angola, the deadliest strain of the Marburg virus, said lead author Thomas Geisbert, professor of microbiology and immunology at the University of Texas Medical Branch at Galveston.
The drug, which attacks the genetics of the virus, is "designed to protect against all known strains of Marburg virus, meaning that the approach has broad-spectrum potential in terms of at least protecting against all of the different strains of Marburg," Geisbert said.
The same technology behind the Marburg drug also has been used to create an Ebola medication that currently is undergoing U.S. Department of Defense-funded clinical trials, Geisbert said. Marburg and Ebola are both filoviruses, a family of viruses that cause severe hemorrhagic fever in humans.
One of the largest Ebola outbreaks in history currently is raging through four West African countries. The virus has claimed more than 1,200 lives and infected 2,240 people, according to the U.S. Centers for Disease Control and Prevention.
Breakthroughs like this Marburg virus research provide hope for this and future outbreaks of Ebola, Marburg and related viruses, said Dr. Ambreen Khalil, an infectious disease specialist at Staten Island University Hospital in New York City.
"It seems to me we now have another very effective means of fighting these viruses," Khalil said. "The way this epidemic is spreading in West Africa, this is a good development."
Scientists note, however, that research with animals often fails to yield similar results with humans.
The new Marburg and Ebola drugs are based on molecules called small interfering RNA, also referred to as siRNA or "silencer" RNA.
For a virus to replicate, it must issue blueprints on how to make more of itself, in the form of messenger RNA, said Dr. Bruce Hirsch, an infectious diseases specialist at North Shore University Hospital in Manhasset, N.Y.
"Silencer" RNA disrupts the delivery of messenger RNA, preventing the virus from replicating, Hirsch said. "No messenger means no message and no more virus," he said.
For the new study, researchers infected 21 monkeys with large doses of the Marburg-Angola virus. "We chose the Angola strain because this strain of Marburg virus has been associated with the highest case fatality rates of any strain or species of filovirus, causing 90 percent mortality in man in the largest outbreak of Marburg in 2005 in Angola," Geisbert said.
They then gave the experimental drug to 16 of the monkeys. The treated monkeys were split into groups of four and given the medication at different times -- 30 to 45 minutes after exposure, or at one day, two days, or three days after exposure.
All 16 monkeys given the Marburg drug survived. The five monkeys left untreated died within seven to nine days.
Both the Marburg and the Ebola drugs seem very safe, Geisbert said.
"If I combine the work that we've done on the Ebola product and the Marburg product in at least more than a hundred Rhesus monkeys, I've never seen a single adverse event in one single animal due to the product," he said.
In July, the U.S. Food and Drug Administration placed a hold on human clinical tests for the Ebola medication, which is produced by the Canadian company Tekmira Pharmaceuticals Corp. under the name TKM-Ebola. The FDA asked the company for additional information to ensure the drug is safe at higher doses.
But in the face of the current outbreak, the FDA earlier this month changed its full clinical hold on the drug to a partial hold, enabling the potential use of the drug for people infected with Ebola, Tekmira announced in a press release.
The "silencer" RNA drugs work in a completely different way from the experimental ZMapp drug that has been administered to a handful of Ebola victims with evidence of success, Geisbert said.
Three doctors in Liberia and two American aid workers who received ZMapp all appeared to respond to the drug, showing signs of improvement after receiving it, according to BBC News.
ZMapp uses laboratory-designed antibodies to block the Ebola virus from infecting a cell, Geisbert said, while the new drug he tested prevents Ebola-like viruses from replicating after they have infected a cell.
Future trials could look at combining the two types of medication, following the example set by the drug cocktails that effectively treat HIV infection, he said.
"You've seen a lot of advances with HIV when people started combining treatments that operated by different mechanisms," Geisbert said.
For more on Ebola virus, visit the U.S. Centers for Disease Control and Prevention.
Posted: August 2014