Common Hypertension Drug Useful in Preventing Epilepsy, Seizures

In a recent study published in the Annals of Neurology, a common hypertension drug prevented post-traumatic epilepsy in animal models.

A team of researchers from Ben-Gurion University in Isreal, Charité-University Medicine in Germany, and the University of California, Berkeley studied rodent models that always developed seizures after injury. After receiving losartan (Cozaar), a drug commonly used to treat hypertension, through their drinking water, 60% of the rats remained seizure-free, while the remaining rats experienced about one-quarter of the amount of seizures typically seen in untreated rats.

“This study, for the first time, offers a new mechanism and an existing, US Food and Drug Administration (FDA)-approved drug to potentially prevent epilepsy in patients after brain injuries or after they develop an abnormal blood-brain barrier,” study contributor Alon Friedman, MD, PhD, said in a press release.

Losartan treats high blood pressure by blocking the angiotensin 1 (AT1) receptor, although it also blocks the transforming growth factor-beta (TGF-β) receptor, a support cell in the blood-brain barrier, which is a tight wall of cells lining the veins and arteries in the brain that can be damaged after brain injury.

The researchers’ previous studies have shown TGF-β triggers localized inflammation, which can cause neural misfiring, a characteristic of epilepsy. Now, the team has demonstrated that even though the blood-brain barrier is generally impermeable, the drug crossed through an injured blood-brain barrier when it was needed.

“Right now, if someone comes to the emergency room with traumatic brain injury, they have a 10 to 50% chance of developing epilepsy, and epilepsy from brain injuries tends to be unresponsive to drugs in many patients,” study co-author Daniela Kaufer, PhD, said. “I’m very hopeful that our research can spare these patients the added trauma of epilepsy.”

Friedman developed a system to use magnetic resonance imaging (MRI) to determine whether the blood-brain barrier has been breached in trauma patients. The MRI images may allow doctors extra time to administer losartan, especially because the barrier may only remain open for a few weeks after injury. However, a few weeks may still be enough time.

In a related study, the researchers demonstrated 3 weeks of losartan treatment sufficiently prevented most cases of epilepsy in normal rodents in following months. They noted this finding was particularly important because the drug prevented the development of epilepsy, rather than after-the-fact symptoms.

The researchers said they hope to begin independent experiments in rats to confirm the findings and then progress to human clinical trials within a few years.