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
The investigators were looking for a particular type of cell in the blood -- a kind of stem cell that turns into white blood cells called B-cell lymphocytes.
"Turns out in these MS patients treated with [Tysabri], the number of these blood stem cells is three- to 10-fold higher than you'd see normally under normal physiologic conditions," Major said.
"JC virus is able to infect these blood stem cells as they become a B lymphocyte," he explained. His working theory has been that these infected B lymphocytes then carry the infection into the brain.
To test that theory, the researchers wanted to see if they could find traces of the JC virus in circulating blood stem cells.
And they did. Of 26 patients who were just starting treatment with Tysabri, 50 percent had traces of the JC virus in their circulating blood stem cells. Of 23 patients who had taken the drug for more than two years, 44 percent had JC virus DNA in more than one kind of blood stem cell type. In contrast, only 17 percent of the 18 healthy volunteers had signs of the JC virus in those cells.
"It was somewhat surprising to us that quite a high percentage of individuals had detectable viral DNA in these blood stem cells," Major said.
But what isn't exactly clear is how this could affect their risk of developing PML. Most patients who tested positive for JC virus had only a few copies of the virus, suggesting that they were still at low risk of infection. Patients who had taken the drug for more than two years had higher virus counts than those who were just starting treatment.
"We need to look at additional patients, and follow them for a long period of time," Major said.
Perhaps most concerning, 10 study participants had evidence of the JC virus in their blood but tested negative for antibodies to it. That suggests current tests for the virus may be missing some patients who could be at high risk for PML infection, the authors explained.
An expert who was not involved in the study, which was published online March 25 in the journal JAMA Neurology, said the findings left some questions unanswered.
"Clearly, Tysabri seems to engender the release of JC virus-containing cells from the bone marrow," said Dr. Gary Birnbaum, a neurologist and director of the Multiple Sclerosis Treatment and Research Center in Golden Valley, Minn. "This could explain why risks of PML are high in patients on this drug," he noted.
"What isn't clear is why the risk escalates dramatically after two years, since JC virus-bearing cells emerge early in the course of treatment," Birnbaum pointed out.
Additionally, Birnbaum said it was "disquieting" that researchers found evidence of the JC virus in patients who then tested negative for antibodies to it.
"Thus, testing individuals for exposure to JC virus by measuring antibodies to the virus may be insufficient to fully assess their risks for developing PML," he said.