Genetic testing helps detect risk of progressive multifocal leukoencephalopathy

The use of a genetic risk test for patients considering immunosuppressive therapies associated with the development of progressive multifocal leukoencephalopathy may help reduce disease incidence, researchers report in Frontiers in neurology.

Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal brain disorder caused by the common, often benign polyomavirus 2, also known as JC virus, Eli Hatchwell, MD, Ph.D., co-founder and chief scientific officer of Population Bio Inc., and his colleagues wrote.

i.e. Hatchwell

“There are many conditions and drug treatments that increase the risk of PML, which is normally a very rare condition in the general population,” Hatchwell told Healio.

Hatchwell and colleagues hypothesize that patients may have genetic susceptibility due to the presence of harmful variants in genes relevant to the immune system. In a previous study, they found 19 candidate PML risk variants and validated four in population and matched controls.

“Patients with MS, and possibly other conditions, who are about to start a drug that is on the list of drugs that can cause PML would benefit from testing to verify the variants we have identified” , Hatchwell said.

According to the study, patients with one of the four identified variants are at high risk of PML (OR = 8.7; 95% CI, 3.7-20.6), measures of clinical validity and of utility comparing favorably to other genetic risk tests, such as those for breast cancer screening.

“Whether [a patient tests] positive for one of these variants, then due consideration should be given either to modifying the planned therapy or to caution in how that therapy is implemented with very close clinical monitoring for any signs of PML” , Hatchwell said.

“There are very, very few specific tests based on a person’s genome, and this is one of them,” Hatchwell added. “We would like to see this as an example of precision medicine and how, in the future, the more we know about a patient’s genome, the more we can tailor their treatments.”

The researchers concluded in the study that “simple and inexpensive genetic testing in patients considering medications with a known or suspected risk of PML will prevent future cases.”