An expert in genetics, working with an international research team, has found that girls with a rare form of female-only epilepsy have a deficiency in a certain hormone called allopregnanolone.
The discovery has led to long-awaited drug trials to see if a synthetic form of the hormone can be used as a form of treatment.
The condition, known as Protocadherin 19 female epilepsy (PCDH19), causes patients to experience frequent seizures early in life and to almost always suffer from some form of cognitive dysfunction and autism. It affects 15,000-30,000 girls in the U.S.
Lead researcher Dr. Jozef Gecz, head of neurogenetics at the University of Adelaide in Australia, has worked with the families of girls with this condition from all over the world and says that while the disorder affects everyone differently, in most cases it is highly debilitating.
“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,” said Gecz.
“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.”
In 2008, Gecz was a key player in identifying the responsible gene and mutations in this female-only epileptic syndrome. Gecz said this disorder is unique as it presents almost exclusively in girls while boys with mutations in the gene are not affected.
“We discovered that this condition is caused by an inherited mutation of the protocadherin 19 (PCDH19) gene, located on the X-chromosome,” he said.
Both males and females can be born with this mutation but only girls 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,” Gecz said.
U.S. pharmaceutical company Marinus Pharmaceuticals (NASDAQ: MRNS) is now recruiting affected girls as part of the world’s first clinical trial to test the therapy.
The findings are published in the journal Human Molecular Genetics.
Source: University of Adelaide