A research group has made a breakthrough discovery which could help thousands of young girls worldwide who are suffering from a rare yet debilitating form of epilepsy. The United States pharmaceutical company Marinus Pharmaceuticals is now recruiting affected girls as part of the world's first clinical trial to test the therapy. 

Professor Jozef Gecz, from the University of Adelaide's Robinson Research Institute, was a key player in identifying the responsible gene and mutations in this female-only epileptic syndrome, in 2008 and has now found a treatment for this disorder.

"We discovered that this condition is caused by an inherited mutation of the protocadherin 19 (PCDH19) gene, located on the X-chromosome," says Professor Gecz, Head of Neurogenetics at the University of Adelaide. "And interestingly, both males and females can be born with this mutation but only females suffer from the symptoms of the condition.

"The girls are affected because they have two X-chromosomes, one healthy and one with the PCDH19 mutation, which would usually protect them from a X-chromosome borne disease, but in this case it drives the disorder," he says.

Gecz has worked with the families of girls with this female-only epilepsy from all over the world and says while the condition affects everyone differently, in most cases it is highly incapacitating. 

"This form of epilepsy affects 15,000-30,000 girls in the US and approximately 1000 in Australia," says Gecz. "Girls born with this gene mutation appear perfectly normal in the first few months of their lives but when they reach about eight months of age, they start suffering from debilitating and frequent seizures. The girls also commonly suffer from intellectual disability and autism - it's a truly terrible disease which impacts the whole family.

"Through our current research we found that sufferers are deficient in a hormone called allopregnanolone. We know that hormones play a critical role in this condition because the seizures often stop once the girls reach puberty - however the autism and intellectual disability remain. We expect that the longer we can delay the onset of seizures, the less the sufferer might be affected by the autism and intellectual disability. 

"These finding are so promising that Marinus Pharmaceuticals has commenced a clinical trial to test the effect of a synthetic form of the neurosteroid allopregnanolone, called ganaxolone," he says.

Published in Human Molecular Genetics.