Ebola is a hemorrhagic disease caused by a virus that, like other viruses, cannot be cured – but in theory at least, the virus can be stymied and its proliferation can be curbed. Now a U.S. Army-funded project studying the mechanism of Ebola in monkeys offers fresh hope to sufferers of the disease, which is deadly in 50 to 90 percent of cases, depending on the strain.
“Cure” means to clear the body of the disease. Bacteria, which invade our bodies but live outside our cells, can theoretically be cleared with antibiotics. Not so viruses, which proliferate inside our own cells: The infection cannot be “cured”, at least not without killing our cells and possibly our selves, but it can be treated to some degree.
Yet the study published today in mBio, the online journal of the American Society for Microbiology, may offer fresh – if distant – hope for central and western Africa, the native home of Ebola, that the disease can be frustrated after all.
Using a compound that blocks the expression of a specific Ebola protein called VP24, the scientists managed to protect 75 percent of the rhesus monkeys infected with Ebola – that is, the monkeys survived. A possible conclusion is that blocking this protein from being created could hold the key to developing effective therapies for the disease, the researchers say.
The study was part of a long-term collaboration between the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) with the biotechnology firm Sarepta Therapeutics, a Cambridge, Massachusetts-based biopharmaceuticals company specializing in RNA-based therapeutics.
Frustrating our anti-viral response
The Ebola protein VP24 is very well known and has been fingered in making Ebola so deadly. Scientists have demonstrated that VP24 shuts off our anti-viral response by binding to a certain protein on the outer membrane ofhuman cells, which transports signaling molecules in and out of the cellular nucleus.
Among the signals that VP24 blocks from entering the nucleus is STAT1, which activates genes for hundreds of proteins involved in anti-viral responses. And there you have it.
Viruses replicate by colonizing cells which then stop making proteins that our bodies need and start making new virus particles. If a drug can be found that stops infected cells from making VP24, the Ebola agent “paralyzing” our immune systems would be thwarted.
An isolation room at Rambam Hospital, Israel, preparing for the possible arrival of patients with Ebola. (Photo by Rami Chelouche)
For over a decade, USAMRIID and Sarepta collaborated on developing and testing a class of antisense compounds known as phosphorodiamidate morpholino oligomers (PMOs for short), explains Dr. Travis Warren of USAMRIID. “Antisense drugs are designed to enter cells and eliminate viruses by preventing their replication,” he says.
Antisense drugs block the translation of viral genes, preventing proteins from being made and giving the infected host time to mount an immune response and clear the virus, says Warren.
The team of researchers had already demonstrated, in a previous study published in the journal Nature Medicine, that a combination PMO called AVI-6002 – which blocks genes coding for VP24 and another protein called VP35 – prevented Ebola virus infection in rhesus monkeys.
This time the sick monkeys were treated with an agent that targets VP24 alone; an agent that targets VP35 alone; and an agent that targets both proteins. A fourth group of monkeys were untreated controls.
The results: Seventy-five percent of the monkeys treated against expression of VP24 survived, as did 62 percent of the monkeys treated with the combination. Monkeys treated against expression of VP35 died at about the same rate as the control group, the team said.
“This study shows that targeting VP24 alone may lead to the development of more effective medical countermeasures,” stated Dr. Sina Bavari, USAMRIID’s science director.
The last outbreak of Ebola, in 2014,was the most severe to date, with nearly 22,500 confirmed cases in West Africa and almost 9,000 reported deaths, according to the World Health Organization.
No vaccines exist to date, though last week tests began in Liberia on the latest two candidates: one developed in the U.S. and one in Canada. Front Page Africa reports on controversy in Liberia over testing – in part because volunteers are reportedly receiving $40 compensation to take the shot. Remarkably, some worry the volunteers will be given Ebola, not an immunization against the disease. Others have a not-unrelated worry. Musician Alphonso Wesseh told the website that he took the vaccine and rumors promptly began to circulate that he had died. Also, Wesseh told FPA, “some friends when they see me they say that they are afraid because I went and took virus into myself.”