Scientists from University College London (UCL), UK, have developed a targeted gene therapy that could potentially help individuals with epilepsy reduce their medication and avoid surgery.
Gene therapy — an emerging area in medicine — involves modifying a person’s gene to treat health conditions.
Until now, gene therapies had been targeting neuron activity and were limited by the inability to differentiate between normal and overactive neurons.
In the newly developed gene therapy — the findings of which were published in the journal Science on 3 November — the scientists added a DNA sequence that directs a specific gene to reduce the hyperactivity of neurons involved in epileptic seizures.
“The idea is to use gene therapy to target and modify the neurons only in the affected region of the brain, sparing all the other parts that are not affected,” Dr Gabriele Lignani, associate professor at the UCL Queen Square Institute of Neurology and the study’s corresponding author, told Happiest Health.
This therapy, which has worked in mice models and human neuron cultures, could potentially reach the human clinical trial stage in two to five years.
During an epileptic seizure, there is uncontrolled electrical activity in neurons in specific parts of the brain for a few minutes. Currently, treatment for epilepsy includes medicines or surgery.
“Surgery is an invasive procedure involving removing that part of the brain where the epileptic seizures occur. However, if the affected region is close to the areas associated with speech and motor functions, there is a higher risk of damage,” says Dr Lignani. In addition, while anti-epileptic medications help with seizures, many individuals develop resistance to the drugs.
The scientists at UCL modified the existing gene therapies to specifically reduce the overactivity in the regions of the brain responsible for epileptic seizures.
The researchers directed the inserted gene to target potassium channels that regulate the electrical response in neurons. By adding a DNA sequence called the promoter, they ensured that the inserted gene targets only the excited neurons.
In their experiments, the researchers added the promoter (cfos) and the gene (KCNA1) onto a harmless virus called adenovirus and introduced it into the brains of mice and culture of human nerve cells.
“The promoter feels the transient activity of the neurons,” says Dr Lignani, adding that it only remains active if the neuron is hyperactive and then switches off.
The scientists found that the introduced gene reduced the number of seizures in mice models without affecting their behaviour and cognition, implying that the technique is safer as it did not affect surrounding healthy tissues. They also detected decreased seizure activity in the human neuron culture.
Dr Lignani envisages that this therapy could also help treat other neurological diseases like Alzheimer’s, Parkinson’s, migraines, and schizophrenia, where there is transient hyperactivity of neurons.