Dr. Kurata’s group identifies the mechanisms behind a chemical compound bringing neurons back in synchrony in epilepsy
Dr. Stepheny Zani - 17 December 2025
Dr. Harley Kurata
Neonatal seizures are the most common neurological event in newborns. Repeated episodes of seizures have serious consequences such as developmental delays. While seizures can happen due to a number of reasons, including infections and metabolic disorders, one of the more common causes of neonatal epilepsy are conditions known as channelopathies.
A channelopathy is as the name implies, a problem with a channel that passes information from one cell to another in the form of electrical signals. In the context of epilepsy, the channels are found in cells that control our movement, our emotions, and our thoughts - neurons.
Neurons work by a process of being turned on (activation) and off (deactivation) to transfer information. Maintaining a smooth balance of activation and deactivation is essential for proper brain function. However, when there is a shift in that balance towards activation, chaos ensues that could lead to drastic effects on the brain and the individual. That’s what happens during an epileptic seizure. Over time, this overactivation damages the cells and causes neuron death.
While we may think of information as words, sounds, and sights, our neurons sense information in the form of chemicals. The most important of these are sodium and potassium. As sodium builds up in the neuron, it gets excited with all that information. When the levels are high enough, the cell has no choice but to broadcast that information to the surrounding cells. Once that happens, the neuron is ready to return to its normal state. But to do that it needs to remove potassium from the cell. That’s accomplished through a biological channel known not surprisingly as a voltage gated potassium channel, which everyone calls Kv. When potassium leaves the neuron through the Kv, the cell calms down and the channel closes.
Now just imagine if that Kv channel for some reason closes too fast and the cell doesn't have enough time to calm down before shooting another message. This hyperexcites the neuron and causes an unexpected rise in information sharing. As we all know, too much information - TMI - is never a good thing and in this case, that rise in information sharing can create chaos at the cellular level and significant disorders in the brain.
Depending on which Kv channel is not working properly, a wide range of diseases can occur. For example, type 7 (Kv7) channels have been linked to several neurological disorders, ranging from epilepsy to hearing loss and chronic pain. As for those neonatal epilepsies, the key channel is known as Kv7.2
With this knowledge in mind, scientists have been trying to find drugs that modulate Kv7.2 channels to regulate uncoordinated neurons and prevent the interruption of message delivery, as happens in a seizure. A chemical compound named QO-58 is a known potentiator of Kv7, already studied in the context of pain and epilepsy. However, less was known about the details of the interaction between QO-58 and the Kv7.2 channel.
That’s where Dr. Kurata’s group enters the scene; they wanted to know more about this interaction, as it is an important step to improve drug development targeting neuron excitability. Their work, led by research associate Dr. Richard Kanyo, was published in the British Journal of Pharmacology, where the findings expand our knowledge of the QO-58 mechanism of action.
After treating cells in a dish with QO-58, they first observed that QO-58 has a selectivity for Kv7.2, an important feature for a drug targeting epilepsy. Next, they identified that the mechanism by which QO-58 modulates Kv7.2 is by delaying its deactivation. If the deactivation of Kv7.2 happens more slowly, it means the channel stays open longer. This allows the potassium "brake" to remain active, giving the otherwise uncoordinated neuron enough time to get back in synchrony with the other neurons. As a consequence, message flow in the brain is restored.
Although the potentiation of Kv7.2 is a shared feature between QO-58 and other drugs already used to treat epilepsy, the Kurata team’s work differentiates QO-58 from other compounds by uniquely characterizing its binding site. They demonstrate that conditions involving specific mutations in the Kv7.2 channel might still benefit from this compound, even when others fail.
Understanding the precise details of drug and target interactions is meticulous work. While one could argue that a "one-size-fits-all" approach might lead to a faster cure, these findings are an example that one size DOES NOT FIT ALL. Ultimately, this study highlights the critical need for, and feasibility of, more targeted pharmacological interventions for neurological conditions. Nevertheless, Dr. Kurata’s work goes in that direction and points to a novel drug class that may benefit those with neonatal epilepsy, especially in cases caused by mutations of the Kv7.2 channel.