JC Virus – PML & MS patients taking Tysabri

From Medical News Today dated: Sep.11th.09

A very interesting discovery… that might help better understand and hopefully prevent the development of PML in MS patients using Tysabri.

The virus responsible for PML (progressive multifocal leukoencephalopathy), a rare brain disease that typically affects AIDS patients and other individuals with compromised immune systems, has been found to be reactivated in multiple-sclerosis patients being treated with natalizumab (Tysabri). The findings, led by scientists at Beth Israel Deaconess Medical Center (BIDMC), appear in The New England Journal of Medicine(NEJM).

“This virus – the JC virus, named for the initials of a patient – is found in about 90 percent of the population,” explains Igor Koralnik, MD, the study’s senior author and director of the Human Immunodeficiency Virus/Neurology Center at BIDMC. “But in healthy individuals the virus lies dormant in the kidneys and causes no problems.” Urine samples of healthy individuals may, therefore, show evidence of the benign virus.

But, according to Koralnik, who is also Associate Professor of Neurology at Harvard Medical School and a world leader in the study of PML, among AIDS patients and other patients with compromised immune systems, the JC virus can reactivate and travel to the brain, leading to the development of PML, a destructive brain disorder that may cause numerous neurological symptoms, including dementia, blindness, paralysis, and seizures. There is no cure for PML and more than half of all PML patients die within a year of diagnosis.

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“This was the first time we had seen PML develop in patients with multiple sclerosis,” notes Koralnik. Because natalizumab, or Tysabri, prevents lymphocytes from crossing the blood-vessel wall, some doctors theorized that it was also providing an opportunity for the dormant PML virus to take hold. “The drug appeared to be something of a double-edged sword,” notes Koralnik. “Not only was it keeping dangerous cells from entering the brain, it was also keeping out the protective virus-fighting lymphocytes, thereby leaving patients vulnerable to this dangerous infection.

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Their results showed that measurements of the JC virus in patients’ urine increased from 19 percent (before beginning treatment) to 63 percent after 12 months of using natalizumab. Six months later – 18 months after beginning treatment – blood samples further revealed that the virus had additionally entered the blood cells of 60 percent of these patients. (At 12 months of treatment, only one patient had the virus in their blood.)

“These JC virus measures were higher than viral measures found in patients infected with the HIV virus, and similar to measures seen in patients with full-blown PML,” explains Koralnik.

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Finally, he adds, the scientists made another startling discovery: Further analysis showed that among many of the MS patients using natalizumab, the JC virus that was detected in their urine or blood samples had already acquired the signature changes associated with the virus’s ability to reach the brain and cause PML.

“This pilot study shows for the first time that natalizumab not only prevents the migration of protective T lymphocytes, but it also directly affects the cells’ potency against the JC virus,” says Koralnik. “It further tells us that reactivation and transformation of the virus may first occur in the kidney and that once the activated virus spills into the blood it can easily spread to the brain.”

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“As of July 24, 2009, there was a worldwide total of 13 natalizumab-treated MS patients who had developed PML,” he adds. “We hope that the results of our study will stimulate further research, and that monitoring the appearance of the virus in the blood and urine may allow for early identification of natalizumab-treated patients at risk of developing PML.”

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