A new drug that inhibits neonatal seizures in rodent models could open up new avenues for the treatment of epilepsy in human newborns. Researchers have identify that gluconate a small organic compound found in fruit and honey acts as an anticonvulsant, inhibiting seizures by targeting the activity of channels that control the flow of chloride ions in and out of neonatal neurons.
Neonates are the most vulnerable population to seizures but there is still no effective medication for the treatment of neonatal epilepsy,” said Gong Chen, professor of biology and the Verne M. Willaman Chair in Life Sciences at Penn State and the leader of the research team.
Neonatal epilepsy patients
The incidence of epilepsy is highest in the first year of life; so with two to four infant babies suffering from neonatal epilepsy for every 1,000 live births in the United States. Unfortunately, so far there is no effective drug available that is specifically develop for neonatal epilepsy patients.
Over the past decades, many drugs have been develop to treat epilepsy in adults. However, neonatal epilepsy patients are often resistant to or do not respond to current anti-epilepsy drugs; also long-term use of some of these treatments may have side effects on brain development.
In the current study, Chen and his colleagues demonstrate that gluconate can inhibit seizure activity in neonatal neurons. More importantly, gluconate suppresses seizure activity in neonatal animals; so more effectively than in adults. This is truly exciting because we have finally identified a potential anticonvulsant drug; so that shows preference to inhibit neonatal seizure activity, said Chen.
Food and pharmaceutical industries
Gluconate is already widely used in the food and pharmaceutical industries; hence as an inactive food or drug additive. For example, it can bind with metal ions to form stable gluconate salts; also such as calcium-gluconate, potassium-gluconate, and zinc-gluconate, that are used for the uptake of metal-ion supplements.
Gluconate is a small organic compound that is produce; so through the oxidization of glucose in many plants, fruits, and honey,” said Zheng Wu, an assistant research professor at Penn State and the first author of the paper. “It has minimal side effects when compare to other organic ions. Because of this, our discovery of its anti-seizure function; hence in neonates could have an accelerate path toward therapeutic development; so for use in the treatment of neonatal epilepsy.
The research team found that gluconate inhibits neonatal seizures; so by targeting what are know as CLC-3 chloride channels. These channels mediate a large ion current in neonatal brains; but are less active in adult brains. Gluconate appears to be too large to pass through the small openings of the CLC-3 channels and therefore acts as a channel blocker.
“The similar effects of gluconate and a ketone body in inhibiting both CLC-3 chloride channels; also neonatal seizures may suggest a better treatment; so than a ketogenic diet in suppressing neonatal seizures,” said Chen. Their work also opens a new avenue for other scientists to design even more specific; also potent blockers for CLC-3 chloride channels to treat neonatal epilepsy.”