An experimental drug cured monkeys infected with a close relative of Ebola virus even after they began showing symptoms — the first time such a drug has been shown to work so many days after infection.
The drug, being developed by a Canadian company called Tekmira, saved the lives of 16 monkeys given highly lethal doses of Marburg virus, the researchers report in the journal Science Translational Medicine. Five monkeys that did not get the drug all died within a week.
More important, monkeys survived even when they didn’t get the drug until three days after they were infected, when they were already beginning to show symptoms such as fever, Thomas Geisbert of the University of Texas Medical Branch and colleagues reported.
This might buy time for patients, Geisbert told NBC News. “You don’t have a lot of time. This whole thing is a race with the clock,” he said.
It's the same approach Tekmira is using for its Ebola drug, which has been fast-tracked by the Food and Drug Administration. The company's looking into possibly providing the experimental Ebola drug to patients in the current outbreak affecting West Africa.
There is no cure for either Marburg virus or its close cousin, Ebola. The ongoing outbreak in Sierra Leone, Liberia, Guinea and Nigeria has killed more than 1,350 people and made more than 2,400 sick.
Quick treatment with saline solution and fever reducers appears to help people survive. Several drugs and vaccines are in the works, and one of them, called ZMapp, appears to have helped two infected Americans — Nancy Writebol and Dr. Kent Brantly — as well as three Liberian doctors.
There's been a debate over whether to provide the experimental drugs to the many people suffering from Ebola, but the supply is very limited. Dr. Jesse Goodman, a former top Food and Drug Administration official who is now at Georgetown University, notes that most drugs fail during experimental trials. “Furthermore, using unproven therapies during emergencies, without adequately evaluating their effectiveness, may result in misleading, even harmful conclusions," he writes in the New England Journal of Medicine.
Geisbert and colleagues have been working with Tekmira on several drugs that help animals infected with both Ebola and Marburg. Tekmira started testing its Ebola drug in people but the trial has been put on hold while the company answers questions about potential side-effects.
Many of the drugs completely protect animals when given right after they are infected. This time, the Marburg drug worked even after three days monkeys got a very high dose of the deadliest strain of Marburg, called Marburg Angola. “We walked this out to the point where the animals are starting to get sick,” Geisbert said.
All the monkeys that got the drug lived, and all the monkeys that did not get it died.
If a drug works even after patients start showing symptoms, this gives it more of a chance of working in a real-world situation. People rarely know the moment they’ve been infected with a virus.
“The minute they don’t start feeling well or the minute you detect the virus you can treat them and still protect them,” Geisbert said.
With a rare drug, this can be priceless. “This conserves doses. You aren’t wasting doses on people who don’t have the virus. Then you are not burning up a lot of valuable doses,” he said.
The drug uses bits of genetic material called small interfering RNAs, or siRNAs for short. Viruses kills cells by invading them and taking over their machinery to force them to pump out copy after copy of virus. This drug doesn’t prevent infection, but stops the virus from replicating by attaching to its RNA. “It messes up the blueprint for making more virus particles,” Geisbert said. “It keeps it from reading the recipe and making virus proteins.”
The idea of using siRNA is not new, but Geisbert had been trying it in animals infected with Ebola and it didn’t work. “I was about to give up,” he said. Then Tekmira called and said "it’s your delivery system," he said. Tekmira’s proprietary system wraps the siRNA in a lipid nanoparticle that protects it from the body’s defenses until it can be absorbed by the immune system cells and liver cells that Ebola and Marburg both just happen to infect.
This particular drug is designer-made to treat Marburg viruses. “It is not going to protect against Ebola. We have to take care of that separately,” Geisbert said. But the technology is the same, and Ebola and Marburg are close relatives. Geisbert says he has not seen side-effects in the monkeys he has treated, another good sign.
What he’d eventually like to see is a cocktail approach, like the mixture of drugs that can now suppress the AIDS virus in patients. Mapp Pharmaceuticals' ZMapp drug given to five people is a mixture of engineered antibodies — versions of the immune system particles that the body uses to neutralize viruses before they infect cells.
“Let’s take the antibodies and let’s take the siRNAs and give them at the same time,” he said. Such a combination approach may be the most effective.
No matter what, early detection is also crucial. Once people have been sick for longer than a few days, it’s much less likely they will survive. Ebola and Marburg both have a fatality rate of up to 90 percent, although in the current outbreak about 60 percent of people known to have been infected die.
That’s because the virus damages immune cells and kills cells in the liver that help blood to clot — that’s why patients often hemorrhage. “You just reach a critical point where no drug on the planet is going to protect you because the virus has already done so much damage,” Geisbert said.
The next step will be to see if Tekmira’s Ebola drug can protect monkeys days after infection, Geisbert said.