New therapy could stop seizures in rare epilepsies

A type of gene therapy could help those with rare forms of childhood epilepsy, including Dravet Syndrome. This breakthrough could lead to treatments for developmental epileptic encephalopathies developing from a single genetic mutation. Encephalopathy is when brain function is impaired by a condition such as viral infection or toxins in the blood. Within the brain the gene SCN8A controls a sodium channel that allows neurons to transmit an electric signal. Sodium channels are membranes in the brain responsible for allowing neurons to communicate. Mutated versions of the SCN8A gene can cause these channels to become hyperactive and bring on repeated seizures. This condition is knowen as SCN8A-Related Epilepsy and average inset age is just four months old.
Miriam Meisler is a professor of neurology at U-M Medical School in the US. Her team have studied the condition for many years and are trying new therapies to treat this epilepsy. She says approximately half of these people affected are severely impaired and cannot walk or talk.
The breakthrough using antisense oligonucleotide (ASO’s) which are short DNA or Ribonucleic acid (RNA) molecules enabled researchers to control how much genes communicate with the body. RNA acts as a messenger carrying information from the DNA about specific proteins. By controlling the amount of RNA expressed by the mutated genes, the team found they could reduce its effects on the body.
By using mice with the same mutated gene they were able to develop an off switch for the gene by activating the ASOs. The effect was dramatic and unambiguous says Meisler. We had a four-fold increase in lifespan with added effects of repeated treatments. There was no evidence of low-level seizure activity in the treated mice.
The level of RNA expressed was reduced by half after the treatment. It was also discovered that the technique was effective against other types of epilepsies including Dravet Syndrome.
The team is now carrying out further testing to see how effective they are against other seizure types. The results are published in Annals of Neurology. For the full study visit: https://onlinelibrary.wiley.com/doifull/10.1002/ana.25676.