GABA receptor linked to absence seizures.

A new animal study offers hope of better treatment for so-called "absence" seizures in humans.

Also known as petit mal, this form of epilepsy occurs mainly in children and is marked by seconds-long lapses in consciousness. A child can experience up to 100 episodes a day, during which he or she may seem to stare, often blinking rapidly, or sway slightly before recovering. Frequent seizures can interfere with concentration and lead to problems in school. Fortunately, seizure frequency tends to decline with time; four-fifths of all affected children outgrow absence seizures by age 20.

New findings suggest that these seizures result from an overabundance of receptors for a brain chemical called gamma-aminobutyric [acid.sub.B], ([GABA.sub.B]), according to neurologist David A. Hosford and his colleagues at the Duke University Medical Center and the Veterans Administration Medical Center in Durham, N.C. They describe their work in the July 17 Science.

This study represents "a major advance ... the first step in designing new therapies" for absence seizures, says Robert J. DeLorenzo, a neurologist with the Medical College of Virginia at Virginia Commonwealth University in Richmond.

The anticonvulsant drugs currently used to suppress absence seizures often cause drowsiness, and can effectively treat only about 80 percent of the approximately 100,000 US. children affected by these seizures, Hosford says.

In their study, the Durham researchers determined that specially bred, epilepsy-prone mice, called lethargic mice, have seizures that closely resemble absence seizures in humans. During the seizures, the brains of these mice produced electrical signals similar to those seen in humans experiencing absence seizures. The mice also responded to the same anticonvulsant drugs used to treat people with absence seizures.

Hosford's team then used the lethargic mice to test a theory, proposed last year by researchers in England, linking absence seizures to the actions of [GABA.sub.B] receptors, which help transmit signals from one nerve cell to another. The Durham scientists found that the activity of these receptors directly influenced seizure frequency: Compounds designed to block the activity of [GABA.sub.B] receptors greatly decreased the number of seizures in the lethargic mice, while a compound designed to enhance the activity of [GABA.sub.B], receptors increased the number of seizures.

Close examination of tissue samples revealed that the brains of the lethargic mice contained 26 percent more [GABA.sub.B] receptors than the brains of normal mice. Electrical tests confirmed that overall [GABA.sub.B] receptor activity was greater in the epileptic mice.

Hosford hopes that such research lead to a more tailored therapy designed to attack the mechanism of petit mal and perhaps treat the seizures without producing some of the more unfortunate side effects" caused by current drugs.