Potential epilepsy drug identified

Researchers have identified a new class of drugs that may prevent the development of a common and devastating form of epilepsy.

Temporal lobe epilepsy is particularly debilitating because it strikes the areas of the brain responsible for memory and mood. As a result, patients have impaired awareness during their seizures. Currently, no drugs are available to prevent temporal lobe epilepsy or slow its progression. Working in mice, researchers at Duke University have identified a compound which may change that.

At least some cases of temporal lobe epilepsy are thought to start after a single episode of prolonged seizures that occurs early in life in response to any number of events.
Research has also shown that a brain receptor called TrkB is overactive after an episode of prolonged seizures and could be responsible for turning the one-time event into a chronic disorder.

In a 2013 study, McNamara's group showed this by using a chemical-genetic approach to block TrkB signalling in a mouse briefly following an episode of prolonged seizures. The inhibition prevented later development of epilepsy.

Researchers found that global inhibition of TrkB signalling following seizures boosted the number of dead neurons in the brain of mice.
The TrkB receptor is known to activate several signalling pathways within cells, so researchers wondered whether distinct pathways downstream from TrkB might control its desirable and undesirable effects.

Researchers found that subsequent seizures appeared to be caused by phospholipase C(gamma)1, an enzyme triggered by TrkB activation. Giving pY816, small-protein drug, to mice for just three days following an episode of prolonged seizures reduced both the likelihood and severity of epilepsy many weeks later. The scientists confirmed that the drug was inhibiting activation of phospholipase C(gamma)1 in the mice.