Scientists believe a drug currently used to help arthritis patients might someday help prevent deaths from pandemic strains of the flu, such as H1N1, also known as swine flu. But experts caution that the research is currently in its infancy and the drug has not yet been tested against the flu in humans.
Researchers at the University of Maryland School of Medicine in Baltimore gave lab mice a lethal dose of an H1N1 strain of the influenza A virus – the same subtype as the swine flu. They also gave them “memory” T-cells for that strain. “Memory” T-cells are white blood cells primed to react to and protect you from a particular strain of the flu. They then treated the mice with the drug abatacept (Orencia). This drug, approved by the Federal Drug Administration to treat rheumatoid arthritis, works by preventing activation of white blood cells needed to fight off infection.
In results published in 2009 in The Journal of Immunology, the scientists say this treatment resulted in 80 percent of the mice living, compared to 50 percent for mice that weren’t treated.
One theory about why young, healthy adults have been sickened most severely by the new H1N1 strain is that their immune systems are overreacting to the threat, mounting a response that not only kills the virus but attacks tissues and organs, shutting them down and potentially causing death.
Donna Farber, PhD, the senior author of the study and a professor of surgery and microbiology and immunology at the University of Maryland School of Medicine in Baltimore, says the findings suggest that tempering the body’s immune system response to influenza may reduce more severe symptoms and even death.
“What happens with these mice is they were able to clear the virus, but didn’t get as sick and recovered a lot better,’ Farber said.
Abatacept does not interrupt the immune system’s early attack in the lungs, which helps kill the virus. But it does appear to prevent the “memory” T-cells from overreacting, the reaction that is thought to make patients sick or die. That may prevent tissue damage caused by the immune response, while still allowing the body to get rid of the virus.
Farber says this is a very promising find because it indicates the medicine would help fight any strain of the flu – the seasonal type or a pandemic version like avian flu or swine flu – since it is targeting the immune system, not the virus itself.
“When patients come to us already seriously ill with influenza, our treatment options are very modest. So anything like this, which offers us a glimmer of hope of doing better by our patients in the future, is of course to be applauded,” says William Schaffner, MD, an infectious disease specialist and chair of the Department of Preventative Medicine at Vanderbilt Medical School in Nashville, Tenn.
But other experts say that while this is a provocative first step, much more research is needed before it can be considered as a treatment in humans.
“This is only one piece of the puzzle,” says David S. Fedson, MD, a physician and influenza expert, who has written extensively on pandemic planning.
“I think this is one component on the part of a very complex response and the tissue damage that is the result of that infection. And the overall host response as it affects all the critical organs in the body is what should be the focus of attention in trying to save lives. And it is unlikely that a drug that targets a single molecule is going to be effective in improving overall host response to influenza,” he adds.
Fedson also says a drug like this would not be a great solution to treat a world-wide pandemic in developing countries, where people might have trouble affording it.
Farber says it’s unclear whether this research means that arthritis patients currently taking Orencia are less likely to come down with the flu or to get less severe types of it. “It’s possible. But we really don’t know,” she stresses.
Until there is more research, she says rheumatoid arthritis patients should not deviate from their current treatment if they are taking abatacept.
“The current commercials for Orencia say stop it if you get a flu or become sick. I wouldn’t change that,” Farber says. “Heed the warnings. If you have an infection, stop taking it as advised until more research is done.”
Farber says there are several more stages of research needed before this treatment would be standard for people in a clinic. Next researchers would like to test the drug in mice that have not previously been exposed to the flu virus to see how the drug works once they’re already very sick. She says this is particularly important because right now there is no treatment for influenza if you don’t get anti-viral medication in the first day or two.
“When patients get into the hospital, it’s way too late for anti-virals. What’s making them sick is this ongoing immune response. So if you can target that in the right way, and modulate it, you can save people’s lives. You wont prevent them from getting ill, but you can cure them,” Farber says.
The study was sponsored by Bristol-Myers Squibb, the company that makes abatacept (Orencia), and the National Institutes of Health.