New research has confirmed a strong link between four genetic mutations and progressive multifocal leukoencephalopathy (PML), a rare but often fatal brain infection that can be triggered by dozens of FDA-approved drugs.
PML is caused by the JC virus , a generally harmless virus carried by up to 80% of the population. PML occurs when the virus reactivates and attacks the brain with life-threatening consequences. Researchers have long been searching for an explanation for why the virus leads to PML in some people but not others.
In this study, researchers first demonstrated that four genetic variants were far more common in patients who developed drug-induced PML than in the general population. They then looked for these variants in the ideal control group: MS patients who carried JCV and were taking a high-riskfor years, but who did not develop PML. The results were even stronger when compared to these matched controls.
Nearly 11% of patients with PML tested positive for at least one of the four variants. To put this finding in perspective, these variants explain a higher percentage of PML cases than the well-known BRCA mutations explain breast cancer cases. Additionally, their predictive power exceeds levels that have led the FDA to require genetic screening for other risky medications.
Drug-induced PML is on the rise as more immunosuppressant therapies are developed. In 2021, there were more than 500 cases in the FDA's adverse event reporting system. These drugs are broadly prescribed: In the U.S., nearly 1 million people have MS, another 1.5 million have blood cancers commonly treated with PML-inducing drugs, and 850,000 Americans have received organ transplants.that greatly increase a person's risk of this devastating infection," says Dr.
Dr. Joseph Berger, another independent PML expert and chief of multiple sclerosis at University of Pennsylvania Perelman School of Medicine and lead author for the American Academy of Neurology's PML Guidelines Committee, says,"Determining genetic susceptibility to PML is an extremely promising method of reducing disease risk. A simple inexpensive test may prove revolutionary in this regard.
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