Biogen Idec turns to expert for Tysabri help
To get answers about why two patients taking its new multiple sclerosis drug Tysabri apparently came down with a rare, often deadly brain disease, Biogen Idec Inc. of Cambridge is turning to Dr. Igor J. Koralnik, a 42-year-old neurologist at Beth Israel Deaconess Medical Center who may know more about the disease than anyone else.
Koralnik, a specialist in neuro-infectious diseases and the impact of AIDS on neural health, will meet Friday with other specialists and Biogen Idec executive vice president Burt Adelman to explore if there is a direct link between the patients' drug regimen and contraction of progressive multifocal leukoencephalopathy, or PML.
On Monday, Biogen Idec suspended marketing and distribution of Tysabri and told doctors not to give the drug to any patients after one in a long-term trial died of PML. Another unidentified patient is suspected of having the disease, but the diagnosis wasn't definitive as of yesterday afternoon.
The challenge for Biogen Idec and its partner in Tysabri, Elan Pharmaceuticals PLC of Ireland, is to quickly determine if the two patients' treatment with Tysabri and another multiple sclerosis drug, Avonex, led to the disease.
In an interview, Koralnik said he is the man for the job: He is one of the world's top experts in the rare condition and for the past eight years has studied the disease in a laboratory at Beth Israel Deaconess funded by the National Institutes of Health.
''My whole interest is to determine why some patients survive," said the Swiss native. ''Ten percent survived PML before there were any medications for HIV. Now, with medication, 50 percent survive."
PML, Koralnik said, was first identified in 1958 at Massachusetts General Hospital. The virus that causes the disease was isolated in 1971 and is called JC virus after the initials of the patient it was taken from. The virus itself is extremely common. Between 80 and 90 percent of the population harbors the virus in an inactive state, often in the kidneys. But most people have white blood cells that can recognize and destroy the virus before it becomes destructive.
But the virus will become active in patients with compromised immune systems, such as AIDS patients. ''Those who can't mount a cellular immune response have an active disease and progressive, devastating symptoms," said Koralnik.
In MS patients, the immune system's disease-fighting T cells migrate into the brain, where they attack the myelin, an insulating sheath covering nerves. Tysabri works by blocking the chemical signal that enables the immune cells to cross the blood vessel wall.
Some doctors theorize that when Tysabri keeps the disease-fighting cells out of the brain -- to prevent MS symptoms -- that provides an opportunity for the dormant PML virus to take hold.
Koralnik received his medical degree at University of Geneva Medical School in 1987. He later served as a post-doctoral fellow in the lab of Robert C. Gallo at the National Cancer Institute. Koralnik performed his residency in neurology at Brigham and Women's Hospital from 1993 to 1996.
Like MS, PML causes damage to the myelin sheath on neurons. But the two diseases look different in MRI scans. Koralnik said he will need to examine MRIs of the two patients diagnosed with PML. ''I can't tell you what PML looks like in an MS patient because nobody has ever seen that before," he said.
Some doctors said that if the risk of developing PML during treatment with Tysabri and Avonex can be quantified, it may make sense to put Tysabri back on the market.
''Multiple sclerosis can be a horrible condition," said Dr. R. Philip Kinkel, director of the Multiple Sclerosis Center at Beth Israel Deaconess Medical Center. ''Some patients commit suicide. If a person's at the point where they'll take their own life because of this, they'll be ready to take a small risk to receive a promising treatment."
Jeffrey Krasner can be reached at krasner@globe.com.
