Currently, when a patient experiences a harsh round of potentially lethal brain seizures, doctors treat the disorder by damping down brain activity. It usually works, but it’s far from ideal.
Now, though, researchers at Northwestern University in Evanston, IL, say that there could be a simple therapeutic approach to managing brain seizures. Observing that severe brain seizures called status epilepticus triggered the production of estrogen in the hippocampus of rats, the investigators determined that drugs that blocked estrogen synthesis were able to quickly rein in the seizures.
They concentrated on two aromatase inhibitors, fadrozole or letrozole (the breast cancer drug Femara), which could do the work.
"As estrogens are known to increase the activity of cells in the hippocampus, estrogen synthesis during seizures could contribute to this activity, making the episodes worse," says author Catherine Woolley in a news release. "Our findings show that breaking this cycle with aromatase inhibitor therapy may be a novel approach to clinically controlling seizures.”
Estrogen also plays a protective role for neurons, causing some concern among the team that their approach could do more harm than good. But the drugs they used produced none of the possible side effects in rats.
"Given the unacceptably high mortality rate of status epilepticus in humans, these findings are likely to elicit great interest by physicians in the field,” noted Stephen Smith, professor of medicine at Oregon Health & Science University, and Director of Medical Critical Care at the VA Portland Health Care System, in the release. “They will hopefully also trigger clinical trials to determine the efficacy and safety of currently available aromatase inhibitors in patients with this condition.”
The work has implications for at least one biotech, Sage Therapeutics ($SAGE), which has been active in the field. SAGE-547 is in late-stage studies for super-refractory status epilepticus.