Researchers in China used a combination of experimental gene therapy and medication to reduce epileptic seizures by more than 90% in three patients with epilepsy resistant to conventional treatments.
Their findings, published in The New England Journal of Medicine on November 4, detailed how electrical activity in the patients’ brains was regulated using a combination of gene therapy and an existing antipsychotic drug.
There was an average reduction in seizure frequency of 92.6% across all three patients following treatment. The trial was much smaller than other studies, primarily because it was intended to assess safety.
Epilepsy is a neurological condition in which abnormal electrical activity in the brain causes recurrent seizures. While it can be controlled with medication, the participants in the trial had epilepsy that was resistant to drugs, a condition that may require surgery or other treatments to manage.
How the treatment works
All three patients had hippocampal sclerosis, a condition involving scarring of the hippocampus, a region of the brain associated with memory. All three had scarring on only one side of their brains and had lived with epilepsy for between 10 and 25 years.
The researchers used an approach called chemogenetics, in which the activity of genetically modified nerve cells can be controlled by administering a specific drug. This allows greater control over the treatment’s effects compared with other gene therapies, as the dosage of the drug can be adjusted.
During surgery, the researchers delivered an engineered virus called adeno-associated virus 9 into the affected region. The virus introduced a gene into neurons that made them responsive to clozapine, an antipsychotic medication.
The modified neurons become less active when exposed to clozapine, helping suppress the abnormal electrical signals that cause seizures. Clozapine was administered to the patients in low doses every eight hours, starting two weeks after surgery.
Seizures decline sharply
Around two months after treatment, the average monthly seizure frequency fell from 4.5 to 0.5 in two participants. In the third, it dropped from four seizures per month to none at all. The researchers also observed no serious adverse effects from the treatment.
“It’s exciting that there’s such a dramatic effect, and that they see very few side effects,” Matthew Walker, a neurologist at University College London who was not involved in the research, told Nature.
However, he raised concerns about the small trial size and the long-term use of clozapine, which has been associated with cardiovascular problems and other adverse effects at higher doses.
“In the future, hopefully there are going to be better drugs,” he said.
The lack of a control group also makes it difficult to determine whether the improvements were solely due to the chemogenetic treatment. Further trials involving more patients will be necessary to determine the treatment’s safety and efficacy.
(Edited By Raunaq Lekhi)