A Potential, Novel Target for Anti-Epileptic Drugs

What is the problem the scientists were trying to solve?

Temporal lobe epilepsy (TLE) is a condition where seizures originate from the temporal lobe of the brain. One of the causes of TLE is an initiating event like meningitis or a penetrating head injury, e.g., a motor vehicle crash. The initiating injury can be followed by a “latent” period when no overt seizures occur. This period can last for months to years, and involves a phenomenon called “epileptogenesis.” In some individuals, the latent period can be followed by spontaneous, recurrent seizures, or epilepsy.

Drugs used for epilepsy are known as anti-epileptic drugs (AEDs). Although these drugs do control seizures in most individuals, they are associated with three main problems. The first is that currently existing AEDs do not target the latent period. If we had a drug that halts epileptogenesis, we could effectively stop epilepsy. The second is that AEDs fail to work in one-third of people with epilepsy (these patients are known as “refractory”). A third, related issue is that all AEDs act via a few known targets. If we had more effective targets, we could possibly design drugs to reduce seizures in the refractory population with fewer side-effects. The scientists of a recent study wanted to know if the TrkB kinase system could be a novel, alternative target for development of AEDs.

How did the scientists approach the question?

TrkB is a receptor protein that has important functions in the brain; and experiments show that TrkB receptor may be important in epileptogenesis. To examine whether TrkB could be a viable new target for AEDs, the scientists needed two main tools.

1. a way to simulate seizures in the lab; and
2. a way to selectively increase and decrease TrkB function.

To simulate seizures, the scientists used a model in mice known as “kindling.” Transgenic mice that had an increase or decrease in TrkB function were used to study effects of TrkB. The experimental design entailed asking how mice with a selective increase or decrease in TrkB function respond to seizures in the kindling model.

What did the scientists find?

Using transgenic mice, the scientists found that mice with more TrkB had more seizures; whereas mice with a lower amount of TrkB had fewer seizures.

What do these results mean?

These experiments are preliminary, but suggest that the TrkB system could serve as a new target for development of AEDs. Although more experiments need to be done to confirm these results, this study certainly suggests that TrkB receptors are worth further exploration.