A Better Gene Therapy for Epilepsy
Last Week in Medicine
Epilepsy is a condition that occurs in brains that are prone to seizures. It occurs when cells in one or all parts of the brain create an abnormal electrical signal. Traditionally, it is tried to be controlled with drugs called anti-epileptics, that is, do not cure epilepsy, only prevent the development of seizures. The working principle of these drugs is to change the level of chemicals in the brain. They block sodium channels in neurons or increase the function of GABA, which suppresses neuronal excitability. Unfortunately, anti-epileptic drugs do not work in 30% of patients. Therefore, experimental treatment methods for epilepsy are being investigated.
One of these methods is gene therapy. In order to stop the onset of epilepsy or lessen the frequency or severity of seizures, gene therapies depends on viral or non-viral vectors to transfer DNA or RNA to specific brain regions where seizures occur. These therapies are being trialled on the principle that targeting these seizure-causing sites will suppress the next seizure. A disadvantage of gene therapy is that it cannot distinguish between a diseased neuron and a healthy neuron in the area treated. Treating only diseased neurons gains importance in terms of the side-effect profile of the therapy.
In a new study published in the journal Science, Qui et al. were able to distinguish neurons that cause seizures from healthy neurons. For this, they talk about a gene therapy that they tested on models of epilepsy. This gene, called Fos, is upregulated by neuronal activity such as seizures. As a result, the expression of Kv1.1 potassium channels, which is an anti-seizure channel, increases.
To test this gene therapy, they produced an adeno-associated virus (AAV) vector that would increase the expression of the Fos gene and potassium channel. They inject this AAV vector into the mouse hippocampus. They then trigger seizures in this area. In their further follow-up, they see that seizures drastically fell off in number.
To test whether their findings would be effective on humans, Qui et al. also applied the gene therapy in human-brains in a dish. In this model, they’ve seen their therapy work, but they say it’s a very distant model from the human brain, so in principle it might be effective.