You might say: 50 million people in the worldPeople with epilepsy. The majority of epileptics can take medication to manage their seizures. However, approximately one-third are not able to respond to these medications.
The only way to stop seizures in such situations is to use force. Take out the brainSeizures can occur. However, this procedure can prove to be very risky.
Epileptic seizures can be prevented by turning off excess activity in brain cells (neurons).
We developed a novel gene therapy method that allowed us to prove in animal and cell cells that it was possible to use this approach. Particularly target the neuronsThey can lead to epileptic seizures.
This stopped them from becoming hyperactive and causing seizures.
This discovery is important for the treatment of drug-resistant epilepsy. It may also have implications for other neurological conditions due to overactive neurons. Parkinson’sMigraines, disease, and other conditions.
Gene therapy
Gene therapy is a method of directly changing a person’s genes to treat a condition or disease. There are many ways to do this.
Previous studiesThe use of a gene therapy technique to treat epilepsy in animal models has been used by those who have successfully used gene therapy. ViralThis virus has been modified in the lab to be safe. Researchers would inject the virus in the brain area where seizures occur.
The virus would then implant stretches of DNA into the cells, effectively modulating the way they worked – Making them less active and preventing seizures.
While this technique is far less invasive than brain surgery, the problem with the method is that it affects all the neurons in the brain region – not just those causing the seizures.
It permanently alters the properties and functions of cells that receive the DNA virus. This can lead to permanent brain dysfunction.
However, our new gene therapy tool shows that it’s possible to modify only brain cells that cause seizures and leave the surrounding healthy neurons intact. This was possible by using the normal regulation of gene expression.
Promoters and their role
Each of the 20,000 genes in our bodies contains instructions for making different proteins and molecules. These genes are often controlled by nearby DNA stretches, known promoters. These control how much and what kind of protein is produced. Different promoters can have different effects on the expression of proteins in cells.
There’s also a special type of promoter (called “activity-dependent” promoters) that will only switch on in response to biochemical signals made by neurons when they fire intensely – such as during a seizure.
These activity-dependent promoters were used to create a gene therapy that reduces the excitability of seizures-causing neurons. This was done by attaching activity-dependent promoters with DNA sequences that include proteins which calm down neuronal activity.
First, we tested the gene therapy tool on neurons in a dish. Then, it was tested on mice with drug-resistant epilepsy. This method was also tested on “mini brains”, lab-grown human cells.
We were able show that this gene therapy technique is effective in controlling seizures-related overactive neurons. Healthy bystander cells are not affected.
Although it takes an hour or so to switch on – longer than the typical duration of a seizure – the new gene therapy is highly effective in preventing subsequent seizures.
It automatically selects which neurons it will treat and switches them off. It can also return neurons to the original state when brain activity returns back to normal. The promoter can switch on if seizures happen again.
The treatment therefore only has to be given once, but has a lasting effect – possibly lifelong.
Importantly, the treatment did no affect the performance in tests of memory or normal behavior (such their anxiety levels, learning and mobility).
This breakthrough is exciting because it could potentially open the door to gene therapy for many people suffering from drug-resistant epilepsy. However, before we can use the therapy with these patients, there will be a series of tests to ensure that it is compatible with larger brains.
Gabriele Lignani, Associate Professor, Clinical & Experimental Epilepsy, UCLAnd Dimitri KullmannProfessor of Neurology. UCL
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