Medicines that change or stop the immune system can be life-saving, but in some cases, they can cause a deadly brain disease. A new study says the problem is in our genetic code.
Medicines that change or stop the immune system can be beneficial for those with cancer and autoimmune diseases, but they can sometimes cause a deadly brain disease.
Progressive multifocal leukoencephalopathy (PML), also known as John Cunningham virus, or JC virus, is a rare and often fatal brain disease.
A new study in Frontiers in Neurology suggests that gene variations in the immune system may significantly increase a person’s risk of developing PML.
The study’s findings may lead to a new set of life-saving genetic testing.
Many important treatments for cancer and autoimmune diseases that change or slow down the immune system can also cause a fatal brain disorder.
The rare and often lethal brain disorder is called progressive multifocal leukoencephalopathy (PML), and a new study suggests that the problem comes from our genetic code.
Scientists worldwide worked together to finish the study, which was published in the journal Frontiers in Neurology.
Researchers found four gene variations in people with PML that affect the immune system. These variations were much less common in the general population that did not have PML Researchers found that these gene variations may increase a person’s chance of getting PML.
Researchers found that PML didn't happen in people with multiple sclerosis (MS) who took medicines that weakened their immune systems, leading them to question why
Before starting the study, scientists first figured out why some patients develop PML and others (the majority) don’t.
In the first study, researchers compared the genes of those with PML to the general population. While the findings were interesting, with the discovery of 19 new gene variants linked to PML, the team decided to focus on a more specific sample group.
For the new study, researchers only looked at those who already had PML or were taking medications that could induce the PML virus. From there, the four different gene variations were discovered.
The team developed a simple genetic test based on their findings. If the test returns positive, a person has about a 20 percent chance of getting PML during treatment.
Genetic testing finds mutations or variants in DNA that may clash with certain medications or treatments. Doctors and scientists use this method to help find the correct dose and type of medicine to treat many cancers, high cholesterol, and other conditions.
According to the researchers, understanding these gene variants could be used to screen patients at higher risk of getting PML from taking certain drugs linked to the disease.
PML is common, with approximately 50 percent of the world's population infected with the virus by age 20. However, most people are asymptomatic, meaning they are simply carriers of the virus.
Overall, symptomatic PML affects only about one in 200,000 people.
The true impact of PML happens when the body cannot fight disease as effectively as it should. When treatments suppress or slow down the immune system, as can happen with many treatments for cancer and autoimmune diseases, PML can become very harmful.
Early symptoms of PML can be mild, and the virus can progress quickly. About 30 to 50 percent of cases become severe within a few months, usually leading to death. Those who survive PML are often left with severe neurological disabilities.
Many drugs already include PML warning labels, but without proper screening of the genes found in the study, it can be challenging to determine the risk for each patient.
Scientists estimate that the study could help cut nearly 10 percent of all PML cases. They are now looking for more variants to protect more patients from PML.
- Frontiers in Neurology. Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies.
- National Organization for Rare Disorders, Inc. Progressive Multifocal Leukoencephalopathy.
- National Institute of Neurological Disorders and Stroke. Progressive Multifocal Leukoencephalopathy.