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University of Maryland researchers work on flu treatment

Scientists say every year thousands of people across the county die from the flu or its complications despite widespread use of the annual influenza vaccines. Researchers at the University of Maryland School of Medicine are pursuing new ways to treat the virus. (Baltimore Sun video)

Modern medicine doesn't offer much to counter the misery brought on by the flu, but researchers at the University of Maryland School of Medicine say they are on to something promising.

It's a protein that not only may ease symptoms of influenza and save lives but protect against other nasty infections.


"Every year, thousands of people across the country die from the flu or its complications, despite widespread use of annual influenza vaccines," said Daniel J. Prantner, a Maryland scientist and lead author of a study about the protein retrocyclin-101. "We think that this protein could lead to medicines that could be a powerful tool in the battle against this disease, and against inflammation in general."

Prantner showed that retrocyclin could prevent immune cells from becoming infected with the flu virus and stop the excessive inflammation responsible for such symptoms as fever, pain, lethargy and troubled breathing.


Retrocyclin works by blocking activation of TLR4, a receptor on human white blood cells that recognizes the impending danger from an infection.

Once TLR4 gets a signal, it tells the cells to respond to the threat and produce inflammation, some of which is necessary to battle an invading virus, bacteria or fungus. Too much inflammation, however, wreaks havoc on the body. When given to sick patients, the retrocyclin would stop the overreaction.

Prantner's study, published recently in the Journal of Leukocyte Biology, demonstrated that retrocyclin shut down the flu in a petri dish full of human cells and in mice.

Another investigator on the project, Alfredo Garzino-Demo from the medical school's Institute for Human Virology, will continue testing it on other infections such as those from Zika, Ebola and dengue viruses.

Prantner said the use of retrocyclin in humans would be years off. One reason: Researchers have to produce a lot of the protein because retrocylcin is not made by the human body; scientists believe it was lost during evolution.

The orangutan is the animal closest to humans that still produces the protein. Researchers make a version of the protein in the lab, a complex and expensive endeavor that is nonetheless likely cheaper than treating the thousands of people who become so sick they seek care in the nation's emergency rooms every year.

Maryland's first seasonal flu cases were confirmed in three adults in the Baltimore area, the state health department announced Thursday. One of those stricken was hospitalized and later released.

The U.S. Centers for Disease Control and Prevention reports that the flu costs $10.4 billion annually for hospitalizations and doctor visits. The agency estimates that hundreds of thousands of people are sickened each year, tens of thousands are hospitalized and thousands die, mostly the very old and very young and those with compromised immune systems.


The agency recommends that everyone 6 months and older be vaccinated for the flu, but fewer than half of Americans do so.

That makes treatment a worthy goal, said Stephanie N. Vogel, a Maryland professor of microbiology and immunology whose lab has been working on the basic science behind possible flu treatments for years.

She has been studying a drug called Eritoran that showed potential in blocking TLR4 during an unsuccessful trial as a treatment for sepsis, a life-threatening response to an infection that leads to blood poisoning and body-wide inflammation.

Vogel hopes to repurpose Eritoran for the flu.

"I'm eager to see what works on the flu but also on emerging viruses such as Zika that are a serious problem," Vogel said. "We'll pursue more than one thing and see what works best."

Antiviral medications such as Tamiflu are currently the only treatment for the flu, she said. They don't reduce inflammation, so they must be given within 48 hours before that overreaction happens. The flu virus is also becoming resistant to the drugs.


There are other efforts underway to find treatments beyond retrocyclin and Eritoran, as well as vaccines for the flu, said Dr. John Treanor, a professor of medicine at the University of Rochester Medical Center in New York and an influenza researcher.

"It's very well recognized that additional treatments for influenza are really needed for many reasons," Treanor said.

There isn't just the human toll from seasonal flu, but the threat of a pandemic — a global outbreak from a new strain for which people have little immunity, he said.

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He said the research across the country centers on the same kind of responses seen with retrocyclin: inhibiting the flu virus from getting into cells and stopping runaway inflammation. Other potential candidates include statins, the cholesterol-lowering drugs, which seem to have anti-inflammatory effects, though it's not yet clear if they work on flu viruses, Treanor said.

As these efforts are underway, other medical researchers and scientists are looking at vaccines. Already, researchers have developed high-dose versions for seniors and vaccines that are produced in cells and not eggs, which can cause allergic reactions.

Treanor, who is now pursuing more effective vaccines, said the ultimate goal is one vaccine that covers a multitude of strains, rather than just three or four at a time, and doesn't require an annual shot.


Until then, the need for treatments remains urgent, he said, though much of the work is still in the lab.

"We have to do the basic stuff first," he said. "It's still early."