Based on these findings, Dr. Alexander is using a two-pronged approach — using resected human brain tissue and an experimental FCD mouse model — to further this research. She's hoping to determine whether neocortical pyramid cells exhibit abnormal bursting behavior, and whether this burst firing pattern is due to alterations in the expressions of T-type calcium channels.
Digging deeper for targeted focal cortical dysplasia treatment options
Discovering T-type calcium channels as the culprit for FCD seizures would be good news for patients, as the channel is a known target for ethosuximide, an FDA-approved drug used to treat some forms of epilepsy.
"As one part of this research, we're taking tissue from FCD patients resected during surgery, slicing it very thin and putting it into an oxygenated environment," says Dr. Alexander. "This allows us to keep the neurons alive and record their activity using a micro-pipette."
However, this approach has limitations due to the lack of normal human brain tissue available, which is why Dr. Alexander's team is also developing a mouse model for exploratory research. Based on a previous model, it uses in-utero electroporation to modulate the mTOR pathway in a subset of neurons, leading to an area of disordered cortical layers similar to that seen in patients with FCD.
Once the model is up and running, Dr. Alexander will study the bursting cells to learn whether the T-type calcium currents play a role in the bursting behavior. If so, her team will test whether the T-type calcium blocker could stop these seizures.
"If we're going to move beyond where we are today, we have to better understand, and then specifically target, the underlying mechanisms that cause different types of epilepsy," says Dr. Brooks-Kayal. "We're thinking beyond seizures."