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New drug offers novel approach to taming flu virus

A drug that flopped in tests to treat sepsis may offer a new way to treat influenza, researchers reported on Wednesday.

If it works in people, it might provide a new defense against emerging new viruses such as the H7N9 bird flu virus circulating in China, other experts said.

Tests in rodents show the drug appears to stop the immune system overreaction that so often kills people infected with influenza and other viruses, the researchers report in the journal Nature. And because it acts on the patient, and not on the virus, it may be immune to the mutations that make so many viruses resistant to drugs.

“We hope it’s a new flu drug,” says Stefanie Vogel, a researcher at the University of Maryland school of medicine who led the research. “This is the first drug to come along for flu where you are not focusing on the virus… What was exciting about our paper is we showed that even starting the drug as late as six days after the infection gave us significant improval in the life of the mice.”

Most strains of influenza have already evolved resistance to the first two flu drugs – amantadine and rimantadine. There are two newer drugs on the market – a pill called Tamiflu and an inhaled powder called Relenza. But there are strains of flu that already elude the effects of Tamiflu.

There’s a third drug, called peramivir, but it’s not widely used. And viruses can evolve resistance to that drug, too.  It’s the same problem that plagues antibiotics, the drugs used to fight bacterial infections. So-called “superbugs” have evolved that can resist the effects of many different drugs.

Health experts are keen for an antiviral drug that will work no matter how the virus mutates. One way to do this is to affect the immune response of the patient.

The new drug, called Eritoran, was originally developed by the Japanese drug company Eisai Co. to fight sepsis. Doctors believe sepsis is a form of immune system overreaction that can kill after an infection or injury.  Eritoran was shown to be safe in people, but it didn’t work well against sepsis.

Vogel’s team had noticed that the drug worked against a particular part of immune system cells called TLR4. They also knew that lab mice genetically engineered to lack TLR4 seemed particularly immune to flu. Could blocking TLR4 make people immune to flu’s effects on the immune system, too, they asked?

It did. Tests in a second rodent called a cotton rat showed this, too. Vogel’s team wants to do further tests but they hope this may provide a new and better way to treat influenza.

Flu usually doesn’t kill people, of course. It just causes unpleasant symptoms such as fever, cough and muscle aches. But it can cause pneumonia and in some people, including perfectly healthy young people, it can cause an immune system overreaction called a cytokine storm. Vogel calls it a cytokine avalanche.

“You need a certain amount of imflammation to be able to fight off the attacking agent,” Vogel said. “But when the inflammation spins out of control, then you end up hurting yourself.”

Joan Nichols, a flu expert at the University of Texas Medical Branch in Galveston, says the study shows Eritoran has a lot of potential. “One of the things we need is a broad-spectrum influenza drug,” she said in telephone interview.

One of the weaknesses of Tamiflu is that it must be taken within a day or two of symptoms showing up to be effective. The new drug might work after people become seriously ill with flu. “This drug could be used to treat people who are already symptomatic,” Nichols said. “You might not see as many deaths.”

A new strain of bird flu called H7N9 avian influenza has already infected more than 120 people in China and killed 27 of them. Tamiflu seems to help, but if the new virus spread and mutated into a form that infected people more easily, it could cause a pandemic. It would take months to make a vaccine, and drugs would be the best defense until one was ready.

“This would be useful in outbreaks like the H7N9,” Nichols said. “No matter what strain of influenza you see emerge, we have got a drug that could buy us some time.”

The approach might also be useful against other viruses that also cause an immune system overreaction, such as severe acute respiratory syndrome (SARS), says John Teijaro, senior research associate at The Scripps Research Institute who specializes in studying these cytokine storms. “Aberrant immune responses have been implicated in the pathogenesis of acute respiratory viral infections including influenza, SARS and hantavirus,” he said in a statement.

SARS, a so-called coronavirus, swept around the world in 2003, infecting around 8,000 people and killing 800 before it was stopped. Health experts are keeping a wary eye on a new type of coronavirus first seen in the Middle East that has killed at least 16 people.

And, said Nichols, the drug has already gone through clinical trials to show it’s safe in people. “Say we needed it tomorrow. They could probably push this,” she said.

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