Seattle scientists seek an Ebola cure
Originally published Saturday, August 2, 2014 at 7:00 PM
Seattle scientists seek an Ebola cure
Two Seattle teams are studying ways to treat the virus and how some people survive the infection that kills so many.
By Sandi Doughton
Seattle Times science reporter
Seattle scientists working on an Ebola cure say the growing outbreak in West Africa lends urgency to their mission.
“To see how fast it’s spreading is incredible,” said University of Washington immunologist Michael Gale Jr. “It shows how dire the need is for antiviral therapy.”
Gale and colleagues at Kineta, a Seattle biotech company, have identified compounds that stop the spread of Ebola and other viruses in laboratory experiments on human cells.
Another local lab, headed by UW microbiologist Michael Katze, is using genetic analysis to understand how some individuals survive the deadly infection and to screen existing drugs for Ebola-fighting ability.
Katze and his team have also helped analyze the body’s response to an experimental Ebola vaccine that proved highly effective in monkeys.
Neither Seattle lab is close to bringing a drug to market, but researchers say the outlook is promising — at least from a scientific perspective.
The biggest hurdles are likely to be economic.
Despite the deaths of more than 700 people in recent weeks, Ebola remains a very rare disease, concentrated in some of the world’s poorest countries, Gale pointed out.
“There’s no money in it,” he said. “American pharmaceutical companies won’t touch anything unless there’s at least a billion-dollar market potential.”
Gale hopes to avoid that pitfall by developing treatments that are effective against a wide array of viruses in addition to Ebola — including flu, West Nile virus, dengue fever and possibly even the common cold.
His team is sharing in a five-year, $8.1 million federal grant to identify compounds that rev up the natural infection-fighting ability of cells, allowing them to repel many types of viruses.
In earlier work, Gale identified an enzyme that is key to activating what’s called the innate immune system — the body’s first-line defense against outside invaders.
The enzyme “turns on literally hundreds of genes that fight off viral infection,” he said.
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Some viruses, like Ebola, have devised ways to dial down that enzyme, explained Shawn Iadonato, chief scientific officer for Kineta.
At the company’s South Lake Union lab, workers screened more than 100,000 chemical compounds for the ability to dial the enzyme up. They identified 20 promising candidates, three of which stood out in follow-up tests.
No labs in Seattle are equipped or approved to work with Ebola virus, so those tests are conducted at a University of Texas facility in Galveston. “There’s a special building with three-foot-thick concrete walls, negative pressure, Pine-Sol showers, all that kind of stuff,” Gale said. Researchers who handle the virus wear respirators and full protective gear.
The next step in the project is to see if the compounds work as well in monkeys as they do in test tubes, Gale said.
The difficulty of conducting human tests with a disease as deadly as Ebola has stalled progress on other promising treatments, including vaccines, said Angela Rasmussen, a UW researcher who works with Katze.
She and her colleagues have developed strains of laboratory mice that mimic human populations in terms of their genetic variability. When the mice are infected with Ebola in experiments at the federal Rocky Mountain Laboratories in Montana, the animals exhibit the same range of symptoms as infected people, including hemorrhage and liver failure.
Most of the mice die. But about 20 percent get sick, lose weight — and then recover.
“That’s what we see in human outbreaks,” Rasmussen said. “Some people can survive, perhaps because they have some genetic trait or immunity.”
By analyzing the mouse genetics in detail and comparing it with the animals’ symptoms and outcomes, the scientists hope to figure out what allows some individuals to recover.
They’re also screening drugs already on the market, to see if they might prove useful. For example, the Ebola virus is known to piggyback into cells on cholesterol molecules, so it’s possible cholesterol drugs could provide some protection.
Though the prospects are good that treatments can be developed, not many U.S. labs are focused on Ebola, Iadonato said. Only a handful are working on broad-spectrum antivirals.
Much of the funding comes under the umbrella of biodefense, out of concern that the Ebola virus could be used as a weapon.
Considering this year’s record-breaking number of cases, the National Institutes of Health decided to fast-track initial human trials on a promising vaccine that worked well in monkeys. But even if the vaccine proves safe and effective, approval wouldn’t come in time to help stem the current outbreak.
Rasmussen, who has assisted in studies on another promising vaccine, would like to see the process accelerated even more.
“This is an emergency situation where peoples’ lives are at stake,” she said. “It’s a terrible human cost, and it’s a terrible way to die.”



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Ebola Cure May Have Already Been Discovered - So Why Are People Still Dying?

The cure for Ebola may have already have been developed by drugs companies, but ethical dilemmas and financial concerns are holding back hopes of a faster cure, scientists have warned.

The worst ever epidemic of the virus, which has swept West Africa, has killed more than 670 people, sparking fears Ebola could move to the UK.

Two people have now been assessed for the virus in Britain, while two American health workers - a doctor and a missionary - have been hospitalised in Liberia after contracting the disease, prompting missionary groups to evacuate non-essential personnel.

But panic grows. Jeremy Farrar, professor of Tropical medicine at the University of Oxford and director of the Wellcome Trust, claimed the mounting death toll was "unacceptable".

"It would be unethical not to acknowledge that potential new treatments could both save lives and reduce transmission in this and future outbreaks," he told the Washington Post.

"We have more than 450 deaths [now it is over 600] so far, and not a single individual has been offered anything beyond tepid sponging and 'we'll bury you nicely'," Farrar told a separate Reuters interviewer. "It's just unacceptable."

Professor Farrar is not alone in questioning whether the West is doing enough to cure a virus that has, so far, only killed people in Africa.

"Farrar is one million per cent right," said Dr Peter Walsh, a biological anthropologist at the University of Cambridge, who has studied the spread of Ebola. "There's absolutely no ethical question involved here. The question is financial and political. To license the drugs that are currently being developed will take years and years. The problem is there is no commercial market in Africa. If this was Western Europe, or North America, we would have a vaccine," he told HuffPost UK.

"There's no monetary incentive for big pharma to put a lot of resources into it. Rest assured, it would have been done if this was happening in England or the US. We would be banging down doors to get to it and get it out to people."

Walsh pointed to the story of a German researcher who accidentally pricked herself with a needle containing Ebola, who was given a vaccine developed in the National Microbiology Laboratory in Winnipeg.

"She had it in her within 48 hours. We don't know, actually, if she ever did contract the disease in the first place but she never developed symptoms. But it shows how they were willing to try the vaccine, and could get it to her quickly," he said.

David Heymann, a professor at the London School of Hygiene and Tropical Medicine, who has studied Ebola since 1976, vehemently disagrees. "There are survivors of Ebola," he told Bloomberg. "Is it ethical to provide a drug when you could be causing a risk to those patients who would survive?

"It would be unethical to roll it out now, in my opinion," said Heymann, a former assistant director general at the WHO.

Dr Heinz Feldmann, an Ebola expert at the US National Institute of Allergy and Infectious Diseases' Laboratories in Montana, told the Canadian Press that he was being bombarded with emails asking why scientists were not pushing out any drug they could. But one colleague had persuaded him it would be a bad idea. "He said 'Anything injectable would be a disaster.'" Feldmann claimed. "He thinks the rumour that we're just spreading the disease is going to be out there before we even start. I think as bad as it sounds — and I really don't feel good about saying this — I have the feeling they have to find a way to end this one without [experimental] therapy."

Ebola is one of the world's deadliest diseases, with up to 90% of cases resulting in death. It is passed to humans through direct contact with the blood, organs or other bodily fluids of victims, meaning doctors and nurses are most at risk. Patients are often overcome by a sudden onset of fever as well as weakness, muscle pain and headaches. Vomiting, diarrhoea, rashes, kidney and liver problems follow. No vaccine or cure is currently available, but several are in development.

One of the US companies named in an informative Forbes piece on Ebola cures is BioCryst Pharmaceuticals, a small North Carolina operation, which is developing a drug called BCX4430 that has proven effective in preventing the death of monkeys were infected with a virus closely related to Ebola.

Why Are There No Drugs for Ebola Virus?
The tests took place with some funding from National Institute of Allergy and Infectious Diseases at a US Army Medical Research Institute, the report into the drug published in Nature, found. All six monkeys infected with the closely-related Marburg virus, which were given the drug one to 24 hours later, were alive 30 days later. All six monkeys who were not given the drug were dead.

"Much of the only real funding now, which is mainly coming from the US department of Defence, is for bio- terror research - it had been thought that it might be used as a biochemical weapon against Americans," Walsh said.

Dr William Sheridan, BioCryst's medical director, told NPR that testing such a drug "just wouldn't make the cut at a major [pharma] company," because the disease has not yet killed a huge number of people, objectively. But he said the company wanted to develop a drug because of the mounting public health concern, and because "there is a market, and the market is the US government."

Rob Bennett, BioCryst’s vice president of investor relations and operations, told Forbes he had had a lot of interest in the drug but it had never been tested on humans. “We don’t see a path to dose patients without at least some fundamental safety data. There would be some ethical issues around that, so it’s a catch-22,” he said.

Paul Hunter, professor of Health Protection at the University of East Anglia, disagrees that there is any ethical dilemma. "As a practicing clinician, if I was given the option to help people with a drug that isn't proven, but has been shown to have at least some effect, it's unethical not to give it to them," he told HuffPost UK.

"In the midst of such a huge epidemic, one could even argue that doing a blind controlled trial would be unethical, because if you give a placebo to some people, who will most likely die, then you are depriving them of a drug that could cure them, something that could save their life.

"It can take months, years for a drug to get approval. By the time it is licensed, maybe everybody will already be dead."

The Canadian Tekmira Pharmaceuticals is also developing a drug to treat Ebola, but the trials were placed on hold earlier this month by the Food and Drug Administration, which requested additional information to ensure the drug is safe at higher doses, according to a Bloomberg report. Additional animal trials are now being conducted until at least 2015.

Mapp Biopharmaceutical Inc, a San Diego company, is another company developing an antibody cocktail similar to the one tested by Canada's National Microbiology Laboratory, according to Bloomberg.

If most scientists agree that trialling even the most experimental drugs would not be unethical, why isn't it happening? Hunter claims it could be lack of supply: "There just aren't enough drugs that exist on the planet to start trying them out. It takes time to scale up what you are producing," he said.

"There also could be many issues around importing the drugs, African countries have been burned before, they've had pharma companies trying to offload totally unsuitable, banned drugs to developing nations."

Source: http://www.huffingtonpost.co.uk/2014/07/30/ebola_0_n_5633405.html