Breast cancer drugs also stop deadly brain seizures, researchers find

John Murphy, MDLinx | May 13, 2016

Researchers have discovered that certain breast cancer drugs can also quickly and effectively suppress serious brain seizures, according to a study published online May 13, 2016 in the journal eLife.

Advertisement

Breast cancer drugs effective at suppressing brain seizures

Injection of an aromatase inhibitor halts a lab rat’s seizure, as seen on EEG (bottom signal). But seizure activity continues in an untreated rat (top signal). (Image: Northwestern University)

“The effect was profound and very clear,” said senior author Catherine S. Woolley, PhD, Professor in the Department of Neurobiology at Northwestern University, in Evanston, IL, who studied the drugs’ effects on seizures in a rat model. “This [study] shows that clinically available drugs could be effective therapies for suppressing seizures in humans.”

This seizure, known as status epilepticus, is a neurological emergency characterized by a prolonged episode of seizure activity. One in three cases don’t respond to first- or second-line treatment, and the overall mortality rate is an estimated 20%. “Thus there is a need for new approaches to acute seizure control,” the authors wrote.

In an attempt to better control these seizures, the researchers experimented with aromatase inhibitors (such as anastrozole, letrozole, and exemestane), which are used to suppress the production of estrogen in postmenopausal patients with hormone-receptor-positive breast cancer.

Prior research has shown that estrogens increase neural activity, while other studies have found that the hippocampus in both men and women can produce estrogen. This suggested to the researchers that estrogens produced in the brain during seizures could also make seizures worse.

“Recognizing that estrogen synthesis during seizures fuels seizure activity gives researchers a specific target for therapeutically breaking the dangerous escalation cycle,” Dr. Woolley explained.

The researchers tested this by injecting rats with an aromatase inhibitor, either fadrozole or letrozole, shortly after seizures began. They found that the aromatase inhibitor strongly suppressed seizures, while untreated control rats continued to have seizures.

The injection not only stopped the seizure, but broke the positive feedback loop that contributed to the escalation of the seizure. “Breaking this cycle with aromatase inhibitor therapy may be a novel approach to clinical control of status epilepticus,” the authors concluded.

Advertisement