People who suffer severe and recurring seizures have few good treatment options, but an experimental drug can reduce seizures in mouse models of two underlying disorders that can cause chronic epilepsy, Yale researchers report in the journal Science Translational Medicine.
Severe forms of epilepsy caused by brain lesions or malformations are usually treated with surgeries and anti-seizure medication. However, the prognosis for many of these patients remains poor, said Angelique Bordey, professor of neurosurgery and of cellular and molecular physiology.
“This is a completely new treatment with unexpected benefits,” Bordey said.
In a study led by first author Longbo Zhang, the Bordey lab reports the elevated expression of actin-cross linking protein filamin A (FLNA) in the brain tissue of many patients with two genetic disorders linked to intractable seizures: tuberous sclerosis complex (TSC) and a subset of focal cortical dysplasia type II. Both disorders are associated with disruption of a regulator of cell growth and cortical malformations with enlarged, dysmorphic cells that are responsible for seizures. Using a drug targeting FLNA to treat mice models of the disorders, Bordey’s lab found that cell enlargement and seizures could be prevented or reduced.
Bordey said her lab plans to explore whether the drug will be effective in treating people with epilepsy and perhaps other symptoms of TSC, such as behavioral problems, including social and intellectual deficits.
The work was primarily funded by the National Institute of Neurological Disorders and Stroke.