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.

Nanotechnology is being studied to develop revolutionary treatments for neurological conditions such as epilepsy. This technology involves the study and development of devices that could control
extremely small objects such as atoms and molecules. Researchers hope that these nanodevices could
could be used as brain implants that control the activity of neurons, reducing or stopping seizures.
The IN-FET project (Ion Neuromodulation Epilepsy Treatment) was launched in January 2020 and has recently been given a 3 Million Euro grant from the European Union. With the approved funding, the will be looking at using nanotechnology and looking at ions such as magnesium, potassium and calcium. These are the chemicals which allow neurons to communicate. Nanodevices could look at and control these ions, and importantly, their concentration. From here it should be possible to change their cell activity, meaning activating or turning off certain neurons. In epilepsy it’s the flow of ions that leads to the burst of electrical activity in the neurons, leading to seizures. Here the nanodevices would act as an ion trap, so they no longer excite the cells, preventing such seizures. Professor Michele Giugliano, is the director of the Neuronal Dynamics Lab at SISSA (Scuola Internazionale Superiore di Studi Avanzati) in Italy. She says Epilepsy is one of the most common neurological conditions affecting 50 Million people worldwide. Drug treatment is a widespread approach to fight it but for many people medication is no help. Epilepsy drugs prove ineffective with the condition. Drug resistance amongst adults ranges between 30% and 40%.
The European project brings together experts in nanoengineering information technology and neurobiology and is funded by the European programme Future Emerging Technologies (FET) Open. The initiative will involve IBM Research, Multi Channel Systems, the Universities of Geneva and Sheffield and the Italian Inter-University Consortium for Nanoelectronics, amongst other parties. The aim of the group will be to develop implantable devices that can alter the concentration of these microscopic ions. These devices will be able to measure the electrical activity of neurons and actively work to correct it.
Todays experimental therapies for restoring or repairing brain functions in neural conditions often involve changing or silencing hyperactive brain circuits explains Professor Guigliano. This can be done with medicines, gene therapy, or electrical or magnetic techniques to affect the brain. However all of these come with serious drawbacks. They unnaturally try and control these neurons. Our idea is to control ions, the very substances that the brain normally uses to function. Through this we’ll be able to discover and test new treatments for epilepsy.
Source Epilepsy Action