Genetic modification of the genes encoding certain proteins that cause epileptic seizures has been described by scientists as an effective tool for treating epileptic children and improving their lives.
The work has the potential to transform the way epilepsy is treated in many ways, and to lead to new treatments that would benefit both children and adults with epilepsy, researchers say.
The research, published in Nature Medicine, was funded by the Bill & Melinda Gates Foundation.
Epilepsy is a common condition that affects more than 10 million people worldwide.
While it can be caused by many things, the most common cause is a lack of the protein that normally controls the activity of the brain.
“We think of seizures as a single thing, but in fact they are a collection of different types of problems,” says study co-author and neuroscientist Prof Peter Hogg of the University of Nottingham, UK.
“There is a lot of variation in the causes of epilepsy, which is a reflection of how we are all different.”
“We have the potential, and the means, to develop therapies to improve the condition,” says Dr Gisela C.M. van Hoorn, a neuroscientists at the University Medical Centre Groningen, Netherlands, who was not involved in the research.
Epidemiologists have identified several genes that are essential for epilepsy, including one that codes for the protein tyrosine kinase (TK).
TK is involved in controlling the movement of electrical impulses in the brain, and in regulating the release of chemicals that cause seizures.
The TK protein has been linked to the development of seizures in some people, but it has not been shown to cause them in others.
“We wanted to see if we could find ways to modify the TK gene and see if it would lead to a different type of seizure in a different patient,” says van Hoort.
In a mouse model of epilepsy in which the mouse was genetically modified to express the Tk protein, a similar type of seizures was induced, with the patient’s seizures subsiding.
This finding was also confirmed in humans.
Researchers also showed that the Tks protein can be induced in mice to suppress the seizure activity of a particular type of brain cell.
After mice were genetically modified in this way, they had a more severe form of the condition called a progressive multifocal cerebral palsy (PFCP), which was linked to a number of genetic variants.
Scientists are now looking at whether the Tkk protein is involved.
While the Tck protein is also involved in seizures, there is no evidence that it controls epilepsy.
There are two main ways to change a gene, says van Hoon.
One is through gene therapy, which involves altering the genetic material of a gene.
Another is through editing genes in a lab.
Epileptogenic mutations in Tkk proteins, for example, cause the body to produce less Tkk.
It is also possible to modify genes that affect the body’s ability to process nutrients and other chemicals.
To study this type of genetic modification, researchers at the National Institute of Neurological Disorders and Stroke (NINDS) and the University College London used mice with mutations in genes encoding the Tkr and Tkr proteins, which have previously been linked with the development and progression of epilepsy.
The Tkk gene was modified to become inactive, which prevented seizures.
The mice also had more severe forms of epilepsy than the controls, including PFCP.
A gene that is critical for the movement and balance of nerve cells was also modified.
All three modifications caused the mice to have more severe seizures.
When researchers examined the mice’s brains, they found that they had more abnormal activity in specific areas of the cortex, a part of the cerebrum.
These areas are known to be involved in movement and coordination, and are known as the motor cortex.
“These are areas where the movements of our muscles and the coordination of our brain functions occur,” says co-senior author Prof Chris Grieve, a neuroradiologist at NINDS.
We thought this might be because these areas are not being used to make a protein, and these are areas of your brain that you can manipulate,” he adds.”
The Tkrs protein is responsible for this, and it turns out that you also have to do something to make the Tkt protein that regulates this movement.
“Grieve says the mice with the Ttk gene mutations were also more susceptible to a type of epilepsy called prion disease, in which abnormal proteins called prions are found in the cerebrospinal fluid.
Prion disease is often fatal.
Experiments with the mice showed that a mutation in the Ttk protein caused the body not to use the Tsk proteins as necessary, and instead to use them to control seizures.”
This suggests that we can