Then Geisbert got an unexpected call. "We would often get calls from 'snake oil salesmen'—people who wanted us to try their products in our models," Geisbert says. Ian MacLachlan, chief scientific officer for the British Columbia–based biotech company Tekmira, told Geisbert about a new delivery system for siRNAs that used SNALPs—stable nucleic acid lipid particles. "I don't know why I gave him a chance," Geisbert recalls.
After MacLachlan and colleagues at Tekmira packaged the siRNAs into SNALPS, Geisbert repeated the guinea pig experiment and waited. Thirteen days after the infection guinea pigs in the control group had died. But those treated with the SNALP-packaged siRNAs were still alive. "It turns out that a lot of the cells that are targeted by Ebola [immune cells like macrophages and dendritic cells] take up SNALP," Geisbert says. "We got 100 percent protection."
Geisbert knew from experience that success in guinea pigs didn't necessarily translate to nonhuman primates (the gold standard in Ebola animal models), which was crucial for developing a human-ready version. Last year, Geisbert and his team decided to test their approach in monkeys infected with the most deadly strain of Ebola—Ebola-Zaire. To increase the chance of success, they included two other siRNAs targeting other viral genes thought to placate the host's immune response, called VP24 and VP35 . They injected the siRNA-loaded SNALPS 30 minutes after injecting Ebola, and then every day for a week. All of the treated monkeys survived and were virus-free after seven days.
Taking it to the finish line
Although this small "proof of concept" study, published May 29 in The Lancet, is only the first of many steps toward a post-exposure Ebola treatment for humans, Geisbert couldn't be more excited. "This is the holy grail for me," he says. "You always want to do something you didn't think could be done. We could never get across that last hurdle of complete protection after exposure." He and his team are already pushing the limits of their treatment. They hope it will be as effective if administered 24 hours after infection—a more realistic time window in an outbreak or lab injury scenario.
But getting the treatment approved for use in humans will be no easy task, Geisbert says. "You're talking millions and millions of dollars to take a product like this across the finish line, and it's a very small market for something like Ebola." Their study was funded by the Defense Threat Reduction Agency, which is part of the U.S. Department of Defense and is dedicated to countering weapons of mass destruction. Geisbert hopes the agency will commit more money for follow-up studies, along with the National Institutes of Health. "This is a great product and I just want to see it do some good," he says.