New Clues to Link Between MS Drug Tysabri and Rare Brain Disease
Researchers report drug mobilizes a kind of cell easily infected by a virus that can attack the brain
By Brenda Goodman
TUESDAY, March 25, 2014 (HealthDay News) -- Researchers report that they think they have figured out why some patients who take the multiple sclerosis drug Tysabri face a high risk of developing a rare, and sometimes fatal, brain infection.
A common virus that can cause the brain disease progressive multifocal leukoencephalopathy (PML) likes to infect and hide in certain blood cells that are mobilized by Tysabri, the study authors explained. Even more troubling, the researchers discovered that current tests may be missing some people who harbor the virus.
Right now, the risk of PML in patients treated with Tysabri for more than two years who also take other immune-suppressing drugs and test positive for antibodies to the virus, "is about one in 75 patients," said study author Eugene Major, a senior investigator at the U.S. National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md. "That's a very high risk."
"We need to be able to understand why this therapy puts patients at risk. As we further define that, we'll be able to develop better tests and better treatment decisions can be made," Major said.
In PML, the normally harmless "JC virus" attacks the white matter of the brain, stripping nerve cells of their insulation. Without this insulation, nerve cells can't effectively carry brain signals. The disease causes progressive weakness, paralysis, changes in vision and speech, and problems with thinking and memory.
According to the NINDS, 30 percent to 50 percent of patients with PML die within a few months of diagnosis. Those who survive the infection may face permanent disability.
Though most people carry the JC virus, PML is rare. It tends to strike people with suppressed immune function, such as patients with AIDS or those taking powerful immune-suppressing drugs like Tysabri.
A combination of three factors seems to put MS patients at highest risk: treatment with Tysabri for more than two years; receiving other kinds of immune-suppressing medications; and testing positive for antibodies to the JC virus.
The drug has had a troubled history. First approved by the U.S. Food and Drug Administration in November 2004, it was pulled off the market three months later after cases of PML occurred in ongoing clinical trials.
Since Tysabri was allowed back on the U.S. market in 2006 with strict prescribing conditions, more than 440 cases of PML have been reported in patients taking the drug, according to the study background. In 2010, the FDA added a warning about the heightened risk of PML to the drug's labeling.
To find out why the drug carries such a high risk of PML, researchers collected blood samples from two groups of MS patients -- those just starting treatment with Tysabri, and those who had been on the drug for more than two years. They compared those samples to blood taken from healthy volunteers.