Gene therapy may protect against flu pandemics - 21 News Now, More Local News for Youngstown, Ohio -

Gene therapy may protect against flu pandemics

Updated: May 29, 2013 03:02 PM EDT
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By Brenda Goodman
HealthDay Reporter

WEDNESDAY, May 29 (HealthDay News) -- Gene therapy that turns cells in the nose into factories that crank out super antibodies against the flu protected mice and ferrets against lethal doses of several pandemic strains of the virus.

If the approach works in humans, it could offer several important advantages over flu vaccines, said study author Dr. James Wilson, a professor of pathology and laboratory medicine at the University of Pennsylvania, in Philadelphia.

Because the therapy can be made ahead of time and fights many different strains, it might give doctors a faster way to thwart flu pandemics.

Currently, doctors race to identify dangerous new types of flu. They then have to develop a vaccine that targets the new strain. The vaccine is then grown in chicken eggs and tested for safety. It takes between three and six months to manufacture large quantities of vaccines against the flu.

"By the time we realize it's a potential pandemic, it's too late," Wilson said. "The timeliness of deploying the seasonal flu vaccine approach for pandemics is not the best way to go."

Vaccines, which prime the body to remember to attack incoming pathogens, also don't do the best job of protecting people who have diminished immune function, such as seniors and those with chronic health problems.

The new treatment, which is delivered through a nasal spray, gets around that problem because it doesn't require the body to mount an immune attack.

Instead, the nasal spray contains many copies of small, harmless viruses called adeno-associated viruses. The simple genome of these viruses can be altered in the lab to carry instructions for making special proteins called broadly neutralizing antibodies.

Broadly neutralizing antibodies are rare super antibodies that are capable of disarming many kinds of flu strains.

When researchers insert the instructions for making those antibodies into the genome of adeno-associated viruses, the viruses act like Trojan horses. They infect cells in the nose, inject the altered genetic material and turn the cells into factories that crank out many copies of the broadly neutralizing proteins.

"The way I envisioned it was sort of a bioshield," Wilson said. "I wanted to focus the production of the antibody to the site where flu enters our body."

In animal tests, researchers showed that mice, ferrets and monkeys made many copies of the super antibody after they inhaled the gene therapy treatment. And the protection seemed to last for a while. Experts note, however, that promising research in animals often does not pan out in humans.

"In mice, it persists up to a year," Wilson said. "In monkeys, we think we're going to see expression up to six months."

The treatment also appears to work pretty quickly. Wilson said the animals were fully protected about three days after their nasal passages were swabbed.

In the test, treated and untreated mice and ferrets were exposed to several different flu strains that have caused worldwide epidemics, including the notorious H1N1 strain that caused the 1918 pandemic, which killed somewhere between 30 million and 50 million people.

"The amount of virus we gave them is 100-fold more than would normally kill them if they weren't treated," Wilson said.

Untreated animals quickly succumbed to the virus, but most animals treated with the gene therapy had some protection against the flu strains they were exposed to. Between 50 percent and 100 percent of the animals survived.

Importantly, 100 percent of the treated animals survived the H1N1 strains that caused the 2009 and 1918 pandemics.

"It really shows that the antibody, when delivered the right way, really has the ability to block infection and prevent disease," said Wilson, who said he has a financial stake in the technology used to deliver the gene therapy.

The study was published in the May 29 issue of the journal Science Translational Medicine.

Other researchers praised the study, but said many questions still need to be answered before it can be used safely in humans.

"It is promising," said Dr. Dimitrios Moskofidis, a virologist and immunologist at Georgia Regents University in Augusta. "The question is, how long could this protection last?" he said, and whether it's safe to coax non-immune cells into making immune proteins.

Study author Wilson said the next step to try to answer those questions involves human pilot studies, in which people would be given the gene therapy treatment and then exposed to weakened flu viruses to see if they get sick.

If it works with the flu, Wilson said, it might work for other respiratory diseases.

More information

For more information on flu vaccines, head to the U.S. Centers for Disease Control and Prevention.

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