The connection between the JC virus and multiple sclerosis (MS) medications centers on a serious brain infection called progressive multifocal leukoencephalopathy (PML). The JC virus (JCV) is a common virus that most people carry without symptoms. It usually remains dormant in the body, but in people with weakened immune systems, such as those taking certain MS drugs, the virus can reactivate and cause PML, a rare but often fatal disease that damages the brain’s white matter.
JCV is widespread—about 70% of adults have been exposed to it—but it only causes problems when the immune system is suppressed. MS medications, especially those that modify or suppress the immune system to control the disease, can increase the risk of JCV reactivation. This is because these drugs reduce the body’s ability to keep the virus in check, allowing it to infect brain cells called glial cells, leading to PML.
Several MS treatments are linked to this risk. Natalizumab, one of the earliest and most effective MS drugs, has a well-known association with PML. The risk increases in patients who test positive for JCV antibodies, have a history of immunosuppressive therapy, or have been on natalizumab for more than two years. Because of this, patients are regularly tested for JCV antibodies before and during treatment to assess their risk.
Other MS medications, such as fingolimod, ocrelizumab, and newer sphingosine-1-phosphate receptor modulators like siponimod, have also been associated with PML cases, although less frequently than natalizumab. These drugs work by altering immune cell trafficking or depleting certain immune cells, which can inadvertently reduce the immune surveillance needed to control latent JCV infection.
When PML develops, symptoms can include weakness on one side of the body, clumsiness, vision problems, cognitive changes, and personality shifts that worsen over days to weeks. Early detection is critical because stopping the MS medication can help the immune system recover and fight the infection. MRI scans can sometimes detect PML before symptoms appear, enabling earlier intervention.
The management of PML involves discontinuing the offending MS drug and supporting immune recovery. However, this immune restoration can sometimes trigger an inflammatory response called immune reconstitution inflammatory syndrome (IRIS), which can worsen symptoms temporarily. Careful monitoring and treatment of IRIS are important parts of managing PML.
Because of the risk of PML, neurologists carefully weigh the benefits and risks of MS medications, especially in patients who test positive for JCV antibodies. Regular monitoring through blood tests for JCV antibodies and MRI scans is standard practice to catch early signs of PML. Vaccinations and other preventive measures are also considered to reduce infection risks during immunosuppressive therapy.
In summary, the JC virus is a latent virus that can cause a deadly brain infection called PML when reactivated in immunocompromised individuals. MS medications that suppress or modulate the immune system can increase this risk by weakening the body’s control over the virus. Careful screening, monitoring, and prompt action at the first signs of PML are essential to managing this serious complication in MS treatment.
