Drug Proves Promising in Pediatric Epilepsy Trial

A drug discovered through an experiment involving zebrafish models was observed to be effective in pediatric patients with epilepsy, according to a new study published in Brain.

“Bench-to-bedside” is a phrase used to describe drugs that moved from animal models to clinical use in humans. These new findings suggest that zebrafish models could be an optimal resource for discovering drugs for human use.

“This is the first time that scientists have taken a potential therapy discovered in a fish model directly into people in a clinical trial,” said Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke. “These findings suggest that it may be possible to treat neurological disorders caused by genetic mutations through an efficient and precision medicine-style approach.”

The team of researchers originally used a zebrafish model of Dravet syndrome to assess the use of lorcaserin in human patients. Once the researchers engineered the zebrafish to develop Dravet syndrome, they found that lorcaserin was able to suppress seizure activity in the fish, according to the study.

Dravet syndrome is a serious form of pediatric epilepsy that is characterized with treatment resistance and developmental delays caused by a genetic mutation. Treatment options for these patients are significantly limited due to the nature of the condition.

The team then tested the drug in 5 children with the seizure condition who were resistant to anti-epileptic drugs. These patients participated in the clinical trial through a compassionate use program, according to the study.

Initially, all children were observed to have reduced seizure frequency. During the first 3 months of treatment with lorcaserin, 1 patient who had previously experienced multiple seizures per day became seizure-free for 2 weeks. However, after 3 months, seizure activity increased, but the frequency was less than at the start, according to the study.

The researchers reported that no patients experienced serious adverse effects, but some reported decreased hunger.

The new findings build on previous studies where the team of researchers screened anti-epileptic drugs, and found that clemizole reduced seizure activity in the zebrafish models. In the new study, the authors found that the drug compound may elicit the anti-seizure effects through modifying the serotonin system.

The investigators then identified a similar drug, lorcaserin, also impacts the serotonin system, but is available for clinical use. Since the drug is available, this may shorten the period of time between clinical trials and use in patients with epilepsy.

“Using zebrafish, we can greatly reduce the time between identification of a potential treatment and getting it to individuals who desperately need help,” Dr Baraban said.

The team of researchers are currently developing clemizole for clinical trials, and are conducting further studies to determine the role of serotonin receptors in epilepsy to develop additional treatment options for pediatric patients with Dravet syndrome.