The life-threatening and treatment-resistant seizure disorder among children known as the ‘Dravet Syndrome’ may soon have new safe and effective therapeutic. The treatment is actually an old drug previously used for obesity in adults and claimed ‘risky’ due to heart failure side-effects. The drug is called fenfluramine and was shown to reduce the occurrence of seizures by more than half among Dravet syndrome patients.
Dravet syndrome develops during infancy and is described as prolonged and frequent seizure episodes that cause developmental delays and speech impairments. About 10 to 15 percent of Dravet patients pass away by age 25 due to seizure related heart problems and suffocation.
"If children with Dravet syndrome can be diagnosed and effectively treated when they are young, they may be spared further neurodevelopmental delays caused by repeated seizures," said co-first author Joseph Sullivan, MD, professor of neurology and pediatrics at UCSF Benioff Children's Hospitals, and director of the Pediatric Epilepsy Center of Exellence. "The results of this study may have significant quality-of-life implications for patients with Dravet syndrome and their families."
Learn more about what it’s like to live with Dravet syndrome:
In the study, participants who averaged 40 convulsive seizures in one month before the clinical trial were randomly assigned one of the three groups: 0.7mg/kg/day of fenfluramine, with a maximum daily dose of 26 mg per day; a lower dose of 0.2 mg/kg/day; or a placebo. Results showed that study participants that received the higher of the two study doses had 62 percent fewer seizure episodes per month than those on the placebo, and those patients who were on the lower dose had 32 percent less convulsive seizures per month than the placebo participants.
Findings of the study were published in The Lancet.
Despite great results, researchers acknowledge why fenfluramine had been taken down from the market by the U.S. Food and Drug Administration in 1997 and that is because of its risk of causing damage to the heart valves.
"This was a concern, but we knew the drug used in this study had undergone tests to enable pediatric use and that patients would be followed closely as part of the study," said Sullivan, who was the principal investigator in the North American study sites. "At the start of the study, when I asked parents what they would do if their child developed heart valve abnormalities, yet had significantly fewer seizures, they said they were willing to accept some risk. They knew that every seizures comes with the risk of sudden unexpected death."
In addition, children were excluded from the trial if they had any heart problems. Although no cases of heart valve damage or pulmonary hypertension was noted, there were some unpleasant side-effects among those that took high doses such as diarrhea, lethargy, and sleepiness. Overall, researchers found out that cases of Dravet patients in Belgium who were clinically on fenfluramine were successful. "Some of these patients have been taking fenfluramine for up to 30 years, with sustained, clinically meaningful reductions in seizure activity without evidence of cardiopulmonary disease," says Sullivan.