A health official checks the temperature of an airport worker in Lagos, Nigeria.

AP PHOTO/SUNDAY ALAMBA, FILE

A health official checks the temperature of an airport worker in Lagos, Nigeria.

The other Ebola debate: What about existing drugs?

Martin is a contributing news editor and writer based in Amsterdam

An ethical panel convened by the World Health Organization (WHO) broke new ground today when it said that using experimental, unapproved drugs or vaccines in the current Ebola outbreak is ethical—assuming a set of criteria is met. There is a big problem, however: None of the experimental therapies and vaccines appears to be available in quantities large enough to treat the thousands in need. One of the issues that needs to be debated is how to fairly distribute the scant resources, the panel said in a statement.

That's why another debate is brewing among some scientists and public health officials: What about trying existing drugs that have been approved for other diseases but that might benefit Ebola patients as well?

Several researchers have floated proposals for trying such drugs. One idea—to try using statins and other widely used, cheap medicines—created a "firestorm" this past weekend after a draft op-ed piece discussing the plan (which was submitted to The New York Times today) was circulated to some 80 researchers worldwide, says Thomas Geisbert, an Ebola researcher at the University of Texas Medical Branch in Galveston.

Geisbert is squarely opposed to the idea, because he says there isn't enough evidence that the drugs would do any good. "I am very, very concerned about this," he says.

But David Fedson, a retired pharma executive living in France who drafted the article together with Steven Opal of Brown University, says there is enough reason to believe that statins and some other used drugs such as ACE inhibitors and angiotensin receptor blockers can save lives and should be tried. Fedson says almost 30 scientists, including very prominent ones, have agreed to co-sign the article.

In Fedson's view, the problem in Ebola is not so much the virus infection itself but a runaway immune reaction that also occurs in the bacterial infection known as sepsis. Statins and other drugs can dampen that immune reaction; a 2012 trial in sepsis patients showed that atorvastatin reduced the risk of progressing to severe sepsis by 83%. He says he has written to WHO Assistant Director-General Marie-Paule Kieny about the idea; she replied with a detailed letter about the agency's reservations, he says. The op-ed article is another attempt to get the issue on the international agenda.

But Geisbert thinks it's a terrible idea. Researchers should be able to show that any therapy taken to Africa has at least prevented death in monkeys, he says—and the drugs that Fedson and Opal are promoting haven’t met that test. "I completely understand that people mean well, and we all want to do something," Geisbert says. "But I have seen so many things that looked promising and didn't work in rodents, or that worked in rodents but didn't protect monkeys. … We shouldn't just grab anything on the back burner" that's approved by the U.S. Food and Drug Administration (FDA) for some uses.

Compounds that change the immune response could actually make Ebola infection worse, Geisbert warns. And if drugs used today in Africa prove ineffective, that could set back the prospects of Ebola drugs as a whole, says Stephan Becker, an Ebola scientist at the University of Marburg in Germany. (Another veteran Ebola researcher at Marburg, Hans-Dieter Klenk, says he has signed the letter, however.)

Fedson says that many scientists who study filoviruses like Ebola have yet to catch on to the idea of treating the immune response. "All they can think about is hammering the virus," he says. (Fedson has also lobbied for years to get statins and other immunomodulatory agents accepted as potential treatment during influenza pandemics.)

Other scientists are trying to get attention for existing drugs as well. Eleanor Fish, a researcher at the University of Toronto in Canada, is hoping to convince WHO and Doctors Without Borders of the benefits of using Infergen, a synthetic interferon α that she has studied and that has been used widely to treat hepatitis C and other diseases. Pharmunion BSV Development, the Ukrainian company that makes it, has offered to ship 60,000 vials to Africa for free, she says.

Fish has long studied the broad antiviral properties of interferon α, and in 2003 she used it on patients infected with another epidemic virus, SARS; a paper she published in The Journal of the American Medical Association reported that it appeared to help them. In an e-mail she sent to officials at Doctors Without Borders and WHO yesterday, Fish cited two papers by researchers at the Public Health Agency of Canada that suggest it can help monkeys survive an otherwise fatal dose of Ebola.

But in those studies, interferon—delivered by an adenovirus—was used in combination with a cocktail of monoclonal antibodies. Geisbert says the efficacy of the mix may have been due to the antibodies; past studies that he and others have conducted have found no effect on Ebola from interferon itself, he says. Fish agrees there is no published evidence that interferon by itself can save monkeys.

Daniel Getts, chief scientific officer of Cour Pharma in Chicago, Illinois, says he has written WHO to suggest the use of his company's Immune Modifying Nanoparticles, designed to reduce tissue damage by binding immune cells called monocytes. The agency has rejected the idea; "they are only interested in therapies with primate data," he says.

Some researchers also see promise in two selective estrogen receptor modulators approved by FDA—one of them is used to treat breast cancer—that were shown to inhibit Ebola infection in vitro and in a mouse model in a 2013 paper in Science Translational Medicine.

Fish says she realizes she's not the only one trying to get the agency's attention. "I imagine people are probably falling out of the trees with all kinds of garlic therapies and who knows what," she says. Indeed, whether WHO has time and resources to look at all of the ideas is unclear; at an 8 August press conference, WHO Director-General Margaret Chan said that her organization is "extremely stretched," as is Doctors Without Borders. WHO's media office did not respond to e-mails today from ScienceInsider about the topic.

The outbreak shows no signs of abating. Today, WHO reported that there have been 1848 cases so far and 1013 deaths; the real numbers almost certainly exceed that tally because some patients don't seek medical care.

*The Ebola Files: Given the current Ebola outbreak, unprecedented in terms of number of people killed and rapid geographic spread, Science and Science Translational Medicine have made a collection of research and news articles on the viral disease freely available to researchers and the general public.

Posted in Africa, Health Ebola