Article, posted on Dravet Syndrome News
A brain protein found on the surface of nerve cells and essential for nerve cell communication is deficient in most patients with Dravet syndrome, but a recent study showed that activating this crucial protein reduces febrile seizures and improves behaviors in a mouse model. The findings support a potential new approach to treat the cause of epilepsy associated with the condition.
Around 80% of Dravet syndrome cases are caused by mutations in the gene (known as SCN1A) that makes this protein (a part of a sodium channel called Nav1.1), and, in most cases, these mutations are not inherited from parents but instead arise during development (de novo). Furthermore, mutations in just one of the two copies are enough to trigger the disease. As such, increasing the production of the protein created from the SCN1A gene may represent a therapeutic strategy to treat the condition.
To this end, one approach is to use a gene editing system known as CRISPR, designed to identify and cut specific regions of DNA. Researchers based at the Nagoya City University in Japan used this technique to target and activate SCN1A gene activity in a mouse model of Dravet syndrome.
While none of the normal mice used as a control had seizures during the test, and untreated mutant mice developed typical Dravet-like seizures, in treated mice, the time until these seizures appeared was significantly longer than in treated mutant mice. Likewise, the abnormal electrical signals found in the brains of Dravet mice, which were absent in normal mice, were decreased significantly in frequency in treated mice. Increased levels of SCN1A activity in the specific nerve cells affected in Dravet syndrome were confirmed in treated mice, along with increased levels of the corresponding Nav1.1 channel protein. Finally, behavioral tests found that treated mice showed improved patterns compared to untreated mice, but not at the same level of normal mice. According to the scientists, the “findings suggest that the decrease in Nav1.1 levels is directly involved in the symptoms seen in adults with Dravet syndrome and open up a way to improve this condition.”