A new small molecule may help people with benzodiazepine-resistant epilepsy. Epilepsy affects an estimated 3.4 million people in the U.S. and millions more worldwide and drugs work for most, but for the rest, Uncontrolled epilepsy and resulting frequent and prolonged seizures lasting five minutes or more that can cause brain cell damage and even death.

Epilepsy occurs when the intricate, delicate balance of signaling by neurons in the brain malfunctions, causing neurons to fire too much and trigger seizures. Benzodiazepines slow down the messages traveling between neurons. Yet up to 30 percent develop drug-resistance after a period of time.

To address that, scientists were looking for targets in the brain that could restore normal signaling. They focused on a potassium chloride co-transporter called KCC2. In the normal brain, KCC2 helps pump chloride out of nerve cells, which helps brake neuronal overfiring. Animal models showed low KCC2 levels and activity in the brain is linked to drug-resistant and prolonged seizures so AstraZeneca screened more than one million compounds to identify a family of compounds that might be able to affect the activity of KCC2 in the brain.

One of the compounds, Compound 350, in combination with benzodiazepine  reduced seizure activity in rodents with drug-resistant seizures. Mice also had lower cell death in the brain than those treated only with the benzodiazepine.

This is only in mice, of course, and mice are not little people despite hype claims in corporate media, Mice studies can only invalidate an effect, never show it, but a lot of great treatments started by first working in mice.