Wednesday, Oct 27, 2021

Rare Tysabri-related Brain Infections May Be Predicted by JC Virus Mutations

By Steve Bryson PhD on Oct 04, 2021 Mutations in the John Cunningham virus may serve as an early predictor for a rare brain infection in multiple..


 By Steve Bryson PhD on Oct 04, 2021 

Mutations in the John Cunningham virus may serve as an early predictor for a rare brain infection in multiple sclerosis patients receiving Tysabri (natalizumab), a study suggests.

However, more research is required to investigate the specific mutations in the viral VP1 gene, and validate the risk of the condition, known as progressive multifocal leukoencephalopathy (PML), in a larger group of MS patients.

The study, “Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab,” was published in the journal Multiple Sclerosis and Related Disorders.

Tysabri is an antibody-based therapy approved to treat relapsing forms of MS. It works by preventing immune cells from accessing the brain and mistakenly attacking myelin, the fatty substance around nerve fibers essential for proper nerve cell function.

Because the therapy suppresses immune responses, more than two years of Tysabri treatment has been associated with PML, a rare and often fatal condition caused by the John Cunningham (JC) virus. Therefore, PML predictive markers would help identify at-risk patients undergoing Tysabri treatment.

While the presence of antibodies against the virus has routinely been used as a marker for PML risk, this often fails to correlate with the onset of the condition. However, mutations in the viral protein VP1 have shown predictive value for PML onset.

In the study, researchers based at the National Institute of Neurology and Neurosurgery in Mexico set out to identify the specific VP1 mutations found in MS patients undergoing Tysabri treatment. They also sought to correlate these results with the anti-JC virus antibody index.

The study included 88 people with relapsing-remitting MS, who had received 31 doses of Tysabri on average (maximum 82 doses), 97 patients with neurological diseases unrelated to MS, and 23 healthy individuals who served as controls. Also included were six people infected with HIV, with three associated with PML.

A total of 60% of MS patients were positive for anti-JC antibodies, with an average antibody index of 2.2. An index of 1.5 or less is considered low PML risk, whereas patients with an index above 1.5 are considered at high risk.

Although the anti-JC antibodies were similar between men and women, a higher level of antibodies was seen in those between the ages of 30 and 39 years (22%). The team found no differences between the time of index evolution (meaningful increases or decreases in antibody index), the number of Tysabri administrations, and previous immunosuppressive treatment.

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By: Stuart[email protected]
Title: JC Virus Mutations May Predict Rare Brain Infection Linked to Tysabri
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Published Date: Mon, 04 Oct 2021 20:19:00 +0000

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