Ganaxolone reduced seizures, anxiety and improved motor deficits in a mouse model of Angelman syndrome, according to a study. That result supports clinical studies to investigate the compound as a possible treatment for this neurological disorder, researchers say..
The study, “Effects of the synthetic neurosteroid ganaxolone on seizure activity and behavioral deficits in an Angelman syndrome mouse model” was published in the journal Neuropharmacology.
Ganaxolone is a laboratory-made steroid that activates a type of receptor in nerve cells’ surface called GABAA receptors. These receptors mediate the inhibition of nerve cells’ impulses by binding to a molecule called GABA, which is the major inhibitory messenger of the central nervous system.
Several studies preformed in Angelman animal models suggest that clinical manifestations of the disease, including seizures and motor disability, result from deficient functioning of a subtype of GABAA receptors, which might be counteracted by ganaxolone.
In fact, treatment with ganaxolone has been able to prevent the occurrence of seizures in multiple animal models of epilepsy, and also was shown to reduce anxiety.
In humans, ganaxolone has been evaluated in Phase 2 trials where it was safe, well-tolerated and able to prevent seizures in adults with partial-onset seizures and epileptic children with history of infantile spasms.
Other trials have been investigating ganaxolone as an anti-convulsant in rare forms of pediatric epilepsy, as a treatment for anxiety in children with fragile X syndrome, and as a therapy for women with postpartum depression.
Ganaxolone has particular advantages as a therapy, including that it can be delivered orally and a low probability of developing treatment resistance, allowing it to be used long-term for the treatment of epilepsy.
Researchers examined the activity of a short-term (three-day) and long-term (four-week) ganaxolone treatment on behavior, neurological function and seizure susceptibility in a mouse model of Angelman.
Both short and long-term treatment with ganaxolone significantly decreased anxiety and improved motor deficits in these animals.
The compound also exerted a therapeutic anticonvulsant effect, reducing by 45 percent and 70 percent the number of seizures in mice treated for three days or four weeks, respectively.
Longer treatment (four weeks) also reduced severity of seizures and improved certain behavioral abnormalities, including motor learning and coordination, and spatial memory.
Importantly, mice did not develop resistance to ganaxolone, as its anti-convulsant activity remained throughout the entire treatment period.
“Our present results indicate that ganaxolone might be particularly well suited as a symptomatic treatment for [Angelman syndrome], with the potential to not only treat the seizures but also to provide long-lasting improvement in the diverse neurobehavioral and motor symptoms.” researchers wrote.
Given the risk seizures pose to children with Angelman syndrome, researchers believe it is worthwhile to determine if ganaxolone can protect these patents against seizures, citing the need for clinical trials.