New Research Generates Excitement About Potential Epilepsy Treatment

Suzanne Paradis
Heratch Ekmekjian
Suzanne Paradis

More than 2 million Americans suffer from epilepsy, as many as 30 percent of them living with medically uncontrollable seizures.

Associate professor of biology Suzanne Paradis and her lab have discovered a novel treatment to reduce seizure activity in mice brains, a breakthrough they hope might one day help people who have epilepsy.

The Paradis lab researches synapses, the connections that allow neurons to transmit electrical or chemical signals. Most synapses are excitatory — they facilitate the passage of signals from one brain cell to another. Others, though, are inhibitory, thwarting transmission.

During an epileptic seizure, the balance between excitation and inhibition goes out of whack, favoring excitation. The result is a kind of power surge where excessive electrical activity causes uncontrolled convulsions, unconsciousness or a temporary loss of awareness.

Several years ago, Paradis and her collaborators pinpointed a protein, Semaphorin 4D (Sema4D), that stimulates production of inhibitory synapses. The researchers showed that bathing mouse brain cells in Sema4D increases the number of inhibitory synapses, ameliorating the signal overload associated with epileptic seizures. These changes happened surprisingly quickly, within minutes.

In its latest research, the Paradis lab, including Daniel Acker, PhD’18; Irene Wong ’17; and Mihwa Kang, worked with mice with symptoms resembling those found in humans with epilepsy. When the researchers infused Sema4D into the animals’ brains, the mice experienced a reduction in the severity of their seizures.

The scientists also observed an increase in the number of inhibitory synapses in the animals’ brains, leading them to conclude that Sema4D treatment increases the brain’s overall resistance to seizures by increasing the number of inhibitory synapses.

“Our idea is simple and has high-impact potential,” Paradis says. “On command, we instruct neurons to assemble more inhibitory synapses in the brain, thus suppressing seizures. This approach could also be beneficial in preventing the establishment of epilepsy, halting its progression or suppressing hyper-excitability during a seizure.”

In humans, Sema4D could be used in combination with current anti-epileptic drugs, such as benzodiazepines, which work by increasing the function of existing inhibitory synapses. Next, Paradis will focus on finding a mechanism, perhaps a drug or gene therapy, to deliver Sema4D to the right target in the brain.

Though it’s unknown whether the strategy will succeed in humans, “the excitement,” says Acker, “is that the general approach works.”