New UF study shows gene therapy could stop seizures
By April Frawley Birdwell
Sparking production of a hormone in the brain that people with epilepsy often lack could prevent debilitating seizures, UF researchers have discovered.
The researchers used gene therapy in rats to stimulate production of somatostatin, a seizure-stopping chemical that naturally occurs in the brain. The study was published in the February issue of the journal Neuroscience Letters.
More than 3 million people in the United States have epilepsy, according to the Centers for Disease Control and Prevention. This lifelong disease is characterized by uncontrollable seizures and can keep people from living independently or holding jobs, particularly if they do not respond to seizure-controlling medication. Finding novel ways to prevent these seizures could help people with epilepsy live more normal, symptom-free lives, said Paul Carney, M.D., chief of the division of neurology in the UF College of Medicine department of pediatrics and senior author of the study.
“For years people have focused only on treating the disease, not preventing the disease,” Carney said. “The mantra is no seizures, no side effects.”
People with epilepsy tend to have lower levels of the hormone somatostatin, as do people with Alzheimer’s disease. Although somatostatin, which belongs to a group of protein-like molecules called neuropeptides, is present in the brains of people with epilepsy, scientists have shown that its levels decrease during seizures, said Rabia Zafar, Ph.D., the lead author and a former postdoctoral associate in Carney’s lab.
To test whether they could prevent seizures by bolstering levels of this hormone, the researchers administered a dose of the gene that triggers somatostatin expression. A harmless virus transported the gene safely through the body.
Boosting somatostatin levels led to weaker and shorter seizures, and none of the subjects that received the injection suffered the highest level of seizure. Better yet, the treatment did not result in unwanted side effects. The only side effect was positive: Subjects learned better after the treatment.
“Being able to restore somatostatin up to normal levels allows the brain to heal itself and that is the idea here,” Carney said. “We’re putting something back in that is normally there and allowing the brain to pick it up as part of its normal machinery. We’re not putting in a drug.”
In addition to epilepsy, studies have shown that somatostatin may play a role in aging and neurodegenerative disorders such as Alzheimer’s disease, Carney said. Somatostatin is a neuromodulator, which means it can alter how nerve cells behave.
In this study, the researchers focused on temporal lobe epilepsy, the most common form of the disease. Although medication helps control seizures in most people with this type of epilepsy, about 30 percent of patients do not respond to therapy, Carney said.
“We need better, more effective treatments for a large population of children and adults who don’t respond to conventional treatments,” he said. “Gene therapy, as well as other forms of treatment, are emerging, and there is the hope and promise they will offer more effective and novel treatments for people with drug-resistant epilepsy.”
But the researchers caution that this study is just a first step. Additional research is needed before the technique can be attempted in humans.