JNS
Direct injection into the brain of a virus carrying a normal SCN1A was found to have dramatic impact on a variety of critical aspects of the disease.
An Israeli breakthrough in the field of genetic therapy stands to revolutionize the treatment of Dravet syndrome, a severe and fatal form of epilepsy affecting children.
The rare syndrome is caused by a non-inherited, random mutation in the SCN1A gene. There is no cure and no effective medication. Dravet also causes developmental delays, cognitive impairment and a high likelihood of premature death. An estimated 15% to 20% of children diagnosed with Dravet syndrome die before reaching adulthood.
Its random occurrence during fetal development makes it difficult to predict or diagnose early on. Seizures typically begin around the age of 1. As the child grows, seizures can last as long as 10 minutes.
However, a team of Tel Aviv University researchers led by Dr. Moran Rubinstein, working in collaboration with other institutions, has developed an innovative gene therapy for the ailment. Their findings were recently published in the peer-reviewed Journal of Clinical Investigation.
As part of the study, a virus carrying a normal SCN1A gene was injected into the brains of mice with Dravet syndrome. The treatment was found to be effective in a variety of critical aspects, such as improvement in epilepsy symptoms, mitigation of early death and significant improvement of cognitive abilities.
Notably, the treatment was found to be effective even after the onset of severe epilepsy in Dravet.
The researchers explained that direct injection into the brain was necessary because the size and properties of the virus do not allow it to pass through the blood-brain barrier. This barrier of blood vessels and tissue helps keep harmful substances from entering the brain.
Some 31 mice were treated at three weeks of age after the onset of spontaneous convulsions—equivalent to 1 to 2 years of age in children. Thirteen mice were treated at five weeks of age—equivalent to approximately 6 to 8 years of age in children.
The injection was performed in several areas of the brain; an empty virus was also injected into the brains of a control group of mice.
The researchers found that the gene treatment’s highest efficacy was at three weeks of age. In these mice, the seizures stopped completely within just 60 hours of injection, life expectancy increased significantly, and cognitive impairment was fully repaired. Even in mice treated at five weeks of age, a significant improvement was observed, with decreased epileptic activity.
For the mice in the control group, no improvement was observed and about half died prematurely.
To test the treatment’s safety, it was also administered to healthy mice, and researchers found no harmful results.
“We hope that the technique we developed in the laboratory will also reach the clinic in the future and help children with this serious disease,” said Rubinstein.
“In addition, since there is a similarity between Dravet and other rare developmental epilepsies, in terms of the patient’s symptoms and brain changes, we hope that this treatment can also help other types of genetic epilepsies, and we think that the tools we developed in this research will pave the way for the development of similar treatments for other rare diseases,” she added.
