What Are They Researching? A Look at Some of Last Year?s Results

By Cara Schmitt
Special to EpilepsyUSA
Posted: July 22, 2003

Talented scientists are essential to finding cures for epilepsy and seizure disorders. For many years, the Epilepsy Foundation and the American Epilepsy Society have funded scientists during the early stages in their careers. This has lead to bringing top-notch scientists into epilepsy research.

Every year, EpilepsyUSA reports on the scientists who have recently been awarded grants by the Epilepsy Foundation and the American Epilepsy Society. Research grant and fellowship recipients who were funded in 2002-2003 are wrapping up their projects, and will be reporting their findings soon.

We are excited about the most recent reported findings of the 2001-2002 grant and fellowship recipients. Many have been published in well-respected medical journals such as Proceedings of the National Academy of Sciences, Neuropharmacology, Epilepsia, Journal of Neuroscience, Neuron, Neuroscience, Journal of Neurochemistry, and Journal of Biological Chemistry.

Having results published in a journal means that a research project is significant enough to share with the medical and scientific community. Frequently, this type of research provides a solid foundation for new medical treatments and therapies. Many researchers have also continued their research through grants funded by the National Institutes of Health.

The research projects during 2001-2002 covered many important areas of epilepsy research. Some looked at the regulation of chemicals in brain cells, the effect of seizures on cells, genetics and imaging. Results from this research have the potential to develop improved medications, to answer questions about how seizures affect the brain, to determine the cause of epilepsy, and to improve epilepsy surgery.

Improving Medications

A major concern for people with epilepsy is to find treatments that will effectively prevent seizures from occurring. But, to develop better medications, one has to understand the intricacies of how brain cells work, what factors interplay to cause seizures and what their role is.

When seizures occur, there is an imbalance of a chemical (ions) across the membrane of the brain cell. Chemicals such as ions move in and out of the cell through channels, helped along by receptors and transporters. Anti-epileptic drugs target these factors to regulate the flow of ions in brain cells to prevent seizures.

A large area of epilepsy research, therefore, is focused on learning more about ions, channels, receptors, and transporters.

There are different types of channels in brain cells. Some Foundation-supported researchers from 2001-2002 looked at potassium channels in the glia (cells that surround the brain tissue). It was found that potassium channels in this area could play a role in the spread of seizures.

The function and expression of a new channel called HCN was also examined. The scientist who did this work has been able to explain how this channel changes throughout life and how its role changes during development. This research was the first to describe HCN’s role in seizures.

Another channel, a chloride channel, was found to be sensitive to seizure activity.

Besides potassium and chloride channels in brain cells, maintaining the correct amount of calcium ions through channels is important. A scientist supported by the Foundation’s research program last year has described how the changes in the structure of a calcium channel could cause seizures. This is particularly significant to the study of absence seizures because this type of seizure is believed to be caused by changes in a calcium channel.

Status epilepticus (periods of non-stop seizures) has also been associated with the loss of needed calcium from inside the cell. Another funded researcher has discovered a mechanism to maintain the proper amount of calcium inside the cell.

Discovering new channels and identifying different ways in which a channel works can help identify new targets for medications.

Receptors are important for “receiving” chemical messages. A cell’s function is often dependent upon receiving a chemical message. The most popular receptor for epilepsy research is the GABA receptor. Basically, the GABA receptor receives the chemical message to either open or close an ion channel.

A scientist has looked at how the GABA receptor fails to respond to traditional anti-epileptic drugs during episodes of status epilepticus. Yet, people experiencing non-stop seizures may respond to other drugs. Through the research, the scientist was able to describe how the GABA receptor changes when seizures occur for 10 minutes or more.

A receptor called a kainate receptor was recently found, and a scientist funded through the research program has examined its role in epilepsy and its function in setting a seizure threshold.

Transporters are responsible for moving chemical messages to the correct place. Two scientists from 2001-2002 funded projects have described new factors that help regulate the glutamate transporter, which in turn, controls the production of GABA—the needed chemical that regulates the ion channels.

Understanding how chemicals move in and out of brain cells is essential to developing new targets for better treatments. Discovering and characterizing the channels, receptors and transporters responsible for the movement of chemicals are crucial steps to achieve this goal.

Effects of seizures on the brain

How the brain responds to seizures and what the impact of seizures is on the brain are major questions for research. To answer them, scientists are examining the ways in which brain cells protect themselves from seizure-caused injury. They are also looking at what causes brain cells to die or function abnormally after many seizures.

Last year, one of the Foundation-supported researchers studied factors that guard against influences that could be damaging to cells. The results from these studies may identify new potential targets for ways to prevent permanent neuronal damage caused by epilepsy.

Another project funded last year examined how the cell protects itself from damage caused by excess calcium. Too many calcium ions, as has been noted, can damage cells.

Other scientists have identified certain proteins that cause brain cell injury. Preliminary research indicates certain epilepsy drugs can slow down neuronal injury. As a result, future research will focus on treatment to prevent seizure induced injuries and examine the benefits of epilepsy medications in people with epilepsy.

Genetics, Technology

Identifying a gene associated with epilepsy aids in determining who may be at risk for having epilepsy.

Last year, a researcher funded through the Foundation’s research program identified specific factors that predict when febrile (fever-related) seizures and epilepsy within the same person and within families. This information may help in identifying who may be at risk for epilepsy, febrile seizures or both. This research will also help find the genes that increase the risk for epilepsy or febrile seizures and aid in genetic studies.

Another way genetics is used to help in studying epilepsy, is by looking at the chemicals produced by a gene. When a gene is turned on or “expressed”, it produces a chemical message. The ability to detect this chemical message is achieved through gene expression technology. This technology is being used to study how epilepsy and many other disorders occur. The idea is to identify the proteins (DNA encoded proteins) in the brain that are present where the seizure begins (epileptic foci) and to compare those areas to areas where seizures are absent. A scientist funded through the research program has identified some of these molecules. This important discovery will provide further insights into how seizures develop. And, in the future, may lead to more effective treatment.

Brain mapping is a technique to identify areas of the brain where seizures occur (epileptic foci). Advances in brain mapping also contribute to improved diagnosis and classification of seizures. Further, progress in brain mapping will increase the effectiveness of surgical therapy.

Two grants last year supported ways of improving brain mapping. One method, optical mapping, increases the understanding of how the epileptic focus is organized. Another method is being developed to make mapping quicker, safer, and able to generate different information from current technology. It also extends to areas of the brain that are not usually mapped.

The results from all of the research projects during this one-year period provide the basis for future endeavors to develop better diagnostics, treatments and therapies. Likewise, the funding provided through the research program is bringing exceptional scientists into the field of epilepsy research and the promise of exceptional progress in the fight to control seizures.