“We got this brain tissue today from Copenhagen. It comes from a patient with very severe epilepsy, for which medication wasn’t helping. The only possible treatment was to remove the part of the brain where the fits were situated”, explains the leader of the research group, Professor Merab Kokaia.
Through a collaboration with neurosurgeons in Lund and Copenhagen, the group gains access to this type of removed tissue. These small clumps of live cells are worth their weight in gold to the researchers. They can be used to study what happens if certain signal substances or nerve cell strengthening substances are added to the cells. Researchers can also see what the diseased brain tissue looks like in great detail.
“In this part of the sample we can see a blood vessel, and here is a scar caused by all the fits the patient has suffered. We can also see that the diseased brain has more of some types of cell than is normal and fewer of others”, says researcher My Andersson.
Compared with other brain researchers, epilepsy researchers are in a better position in this sense. Those who work on stroke, Parkinson’s and Alzheimer’s don’t have any living human cells to work on, because those patients are treated with drugs and not with surgery.
However, in other respects epilepsy researchers are in a worse position. Epilepsy is as common as Parkinson’s in Sweden (see box), but is a considerably less well-known disease. This means that research grants are more limited.
“Unfortunately, there are still many people who are ashamed that they have epilepsy and don’t like to tell the people around them. If they are on medication, it is possible to hide the disease. Those who don’t take medication because it doesn’t help them are often forced to live quite an isolated life”, says Merab Kokaia.
A huge 30–40 per cent of epilepsy patients are not helped by today’s drugs. They can therefore be affected by fits that at worst cause them to collapse without warning. They are not allowed to drive, and other everyday activities such as cycling, walking, swimming and cooking can be dangerous.
Some patients only rarely have fits, whereas others can have them multiple times a day. For the latter group, surgery is the only treatment available – if it is possible.
“For it to work, we have to know exactly where the fits originate, which cannot always be identified accurately. Even if we know, it is not possible to operate on very sensitive regions of the brain. For example, the fits often originate from areas in the hippocampus, which is important for memory and which you therefore have to be very careful with”, explains Merab Kokaia.
New alternatives are needed for those patients who are not helped by either drugs or surgery. This is what the Lund researchers are working on with their three research paths: gene therapy, cell transplants and optogenetics, which involves passing light into the brain.
Gene therapy involves loading harmless viruses with genes for different substances that the epileptic brain is believed to lack. Once the virus has been inserted into the right place in the brain, it makes its way into the nerve cells, which use their new genes to start producing the healthy substances. The treatment principle is already being tested on patients with Parkinson’s disease, and trials on patients with epilepsy could start in a few years.
The trials of cell transplants involve getting the brain to produce substances that make it stop overreacting and causing fits. The transplant could come from the patient’s own skin, the cells of which are treated using various complicated methods to convert them into something resembling stem cells or nerve cells. This technique is still far in the future, because there are a number of questions remaining.
“In all stem cell research, it is important to ensure that the stem cells cannot turn into cancer cells. They must be able to divide, but only in a specific manner. If we instead try to produce nerve cells, the question is how like nerve cells the new cells will actually be. Will they adapt to their new place in the brain and form connections with the surrounding cells?” wonders Merab Kokaia.
The progress of the transplanted cells can be studied with the Lund group’s third and most futuristic research path, ‘optogenetics’. The term refers to the insertion of an optic (light-sensitive) protein into the nerve cells using genetic engineering. When the cells are illuminated, their reaction enables the researchers to see how they work. What is more, it may be possible to control them.
“With the help of light, it may be possible to curb overactive cells or activate slowing cells with millisecond precision. The ideal would be a system that can pick up signals that indicate a fit is developing, and then use light to stop it before it starts”, says Merab Kokaia.
A system of this kind would comprise several parts. Besides nerve cells made sensitive to light, it requires a light source, a sensor that can pick up the preliminary stages of a fit and a battery pack on the outside of the head. The light source could be a small laser connected to a thin optic fibre or a mini LED connected to a thin nanowire. The system would be a sort of pacemaker for the brain, but using light rather than electricity.
The brain pacemaker is a vision that will probably not be realised for a long time yet. In less advanced areas, however, optogenetics is seeing rapid progress. The technology was only invented in 2005 and is being taken up rapidly by research groups around the world.
One of the advantages of optogenetics is that it is so specific. Cells in the brain can also be activated by electrodes, but an electrode affects all the cells in the vicinity, whereas light from an optic fibre only affects the cells that have the light-sensitive protein.
“Because the protein comes from a bacteria, the safety checks are extra stringent if the method is to be used on humans. That is why current optogenetics research uses animal experiments and cell cultures. However, it is an interesting method with great potential”, says Merab Kokaia. He is participating in a large-scale EU project that looks at new ways of treating epilepsy.
INGELA BJÖRCK
