Drug-induced fatal brain infection linked to DNA changes

Eight drugs have a Black Box Warning about PML, the strongest warning issued by the FDA. More than 30 additional medications carry other PML warnings. In total, cases of PML were reported to the FDA in patients taking more than 75 medications. This list includes many of the most effective treatments for multiple sclerosis (MS), blood cancers, rheumatoid arthritis, Crohn’s disease, and organ rejection.

PML is caused by the JC virus (JCV), a generally harmless virus carried by 80% of the population. PML occurs when the virus reactivates and attacks the brain with life-threatening consequences. Researchers have long sought an explanation of why viruses lead to PML in some people but not in others.

In this study, the researchers demonstrated for the first time that four genetic variants are much more common in patients who develop 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-risk drug for many years but did not develop PML. The results were even better when compared with these matched controls.

Do genes play a role in progressive multifocal leukoencephalopathy?

Nearly 11% of patients with PML tested positive for at least one of the four variants. To better understand this finding, these variants explain a higher percentage of PML cases than well-known BRCA mutations that explain breast cancer cases. In addition, their predictability is so overwhelming that the FDA requires genetic screening for other risky drugs.

Drug-induced PML is on the rise as more immunosuppressive therapies are developed. By 2021, there are more than 500 cases in the FDA’s adverse event reporting system. These drugs are widely prescribed: in the US, nearly 1 million people with multiple sclerosis, another 1.5 million with a blood cancer commonly treated with drugs that cause PML, and 850,000 Americans who have had a transplant. organ transplant.

Determination of genetic susceptibility to PML is an extremely promising method for reducing the risk of the disease. A simple, inexpensive test could prove revolutionary in this regard.

Source: Eurekalert


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