Hoping to develop a drug against Ebola, but lacking the $1 billion to bring a new medicine to market, Boston University infectious disease researcher Gene Olinger turned to a more affordable source of drugs — those already available at his local pharmacy.
It paid off. In a study published Wednesday, Olinger reports that he and his team have found two promising possibilities, one a pill used to treat depression, the other taken for heart pain.
Seven of 10 mice infected with a lethal dose of Ebola lived after being given Zoloft (also known as sertraline), commonly used to treat depression, anxiety, obsessive-compulsive disorder, and post-traumatic stress disorder. And all of the Ebola-infected mice given Vascor, a heart drug, survived, according to the new study in Science Translational Medicine.
These drugs are far from a cure for Ebola. They still need to be tested in monkeys and, if they work, then in people. But this screening technique could make a profound difference in the treatment of infectious diseases that may seem minor today, yet could cause the next global outbreak.
“I really like this approach,” said Dr. Daniel Lucey, an adjunct professor of microbiology and immunology at Georgetown University Medical Center. “It’s a big, big plus to already have drugs that are FDA-licensed in terms of the potential speed through which it may be made available.”
For Olinger, the finding culminates a 15-year search for ways to screen drugs to gauge their effectiveness against Ebola, which has killed more than 11,000 in West Africa over the last 18 months.
The researchers surprised even themselves when they found common medications that had an effect against Ebola.
“It was quite shocking to see — antidepressants, cardiac drugs, and drugs that didn’t make a lot of sense initially,” said Olinger, a National Institutes of Health contractor and adjunct professor at BU, where he works at the National Emerging Infectious Diseases Laboratories.
In screening 2,600 FDA-approved drugs over the course of about a year, the team found 80 that showed some activity against Ebola, including antihistamines, breast cancer treatments, heart disease drugs, and antidepressants, said Judith White, a University of Virginia microbiologist who worked on the new study.
She has since helped the team show that many of these drugs work by blocking Ebola from entering an animal cell, essentially filling in the keyholes that Ebola uses to unlock and access its victim’s cells.
“We don’t know in all cases what the antiviral molecular target of these drugs are, but we know in terms of the viral lifestyle what they’re impeding,” she said.
The drugs were put on lab dishes in Cambridge, shipped without names — so as not to bias the research — to a federal lab in Fort Detrick, Md. There, Ebola-infected cells were added to each of the drug-filled dishes and left to grow for 48 hours. Then, the dishes were read by a machine to see whether the Ebola cells had been killed off.
The results, which will be made public, were then interpreted back in Cambridge, at the offices of Horizon Discovery Inc., a global genomics company with offices on First Street.
Then, the most promising drugs were tested in mice, leading to the results showing Vascor effective against Ebola, and Zoloft partially effective. Vascor (also known as bepridil) is a calcium channel blocker.
These are not the first drugs used against Ebola.
Two experimental drugs, ZMapp and TKM-Ebola, were used a handful of times in the ongoing outbreak in West Africa. Both drugs have been extremely effective in treating primates with the disease, but haven’t been tested enough in people to know whether they work, or when they should best be given, or at what dose.
Both also must be delivered by injection and are extremely expensive, which limits their practicality in poor countries such as Liberia, Sierra Leone, and Guinea, places devastated by the current outbreak. Although Liberia is now Ebola-free, pockets of disease still exist in Sierra Leone and Guinea, and health officials say it will still be difficult to eradicate the disease, which likely jumped to people from bats in a forested area of Guinea.
Thomas W. Geisbert, an Ebola specialist at the University of Texas Medical Branch in Galveston, said he is excited about the potential of this screening approach. But he is skeptical that these two drugs would work well in people. He has seen too many medications that looked promising in rodents fail to save monkeys with Ebola. Some of them made the monkeys die even faster, he said.
It will also be difficult to find drugs that work better than TKM-Ebola and ZMapp seem to, Geisbert said.
“Those two drugs are amazing. They’re so far above everything else, they’re ridiculous,” he said. “I never thought you’d see a point where you’d have drugs that would completely, 100 percent protect monkeys.”
Geisbert thinks the two drugs identified by the new study should be tested immediately in monkeys. If they were effective, that would be fantastic, he said, because of the difference in cost and ease of distribution.
Even if they are not as good at reversing the disease, they might be useful in preventing people from contracting the Ebola virus, a role that doesn’t make sense for TKM-Ebola or ZMapp because of their cost, he said.
White and Olinger said they expect a combination of drugs will be needed to combat Ebola. The team is now looking at already-approved drugs in combinations of two and three, hoping to do for Ebola what combination therapies have done for the treatment of AIDS.
White said the one thing that worries her about the screening results is that people will think that if they pop readily available pills, they will be magically protected against a deadly disease.
“I can’t say that it wouldn’t work,” she said, “but we’re not there yet.”