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Researchers discover sugar compound wards off seizures

By Wai Lang Chu , 17-Oct-2006

Researchers have demonstrated that a new compound has the potential to effectively cure epilepsy, raising hopes that a new drug can be produced to treat epileptic patients, who currently have no access to treatment.

About 1 per cent of the world's population suffers from epilepsy, a neurological condition that makes people susceptible to seizures. Scientists believe that seizures occur due to changes in how brain cells send electrical signals to each other.

In about 30 to 50 per cent of epilepsy patients, available treatments - including the removal of parts of the brain's temporal lobe - are largely ineffective.

Researchers at the University of Wisconsin-Madison have been experimenting with 2-deoxy-glucose (2DG) a small, sweet-tasting compound that is normally used in radio labelling, medical scanning and cancer imaging studies in humans.

Researchers injected rats with the substance after previous studies had investigated the role of sugar in controlling seizures.

Early experiments demonstrated that children on sugar-free diets could rapidly experience seizures when they consumed even a small dose of carbohydrates.

The researchers believe that 2DG would work as an effective substitute because it enters cells and clogs up certain cellular enzymes. As a result, the body can't use its own glucose.

"We pumped the rats full [of 2DG] and still saw no side effects," said senior author Avtar Roopra, a UW-Madison assistant professor of neurology.

"I see 2DG as an epilepsy management treatment much like insulin is used to treat diabetes," he added.

Roopra, who estimates that the compound may be available for human use within five years, believes the research also clears up the gap in understanding the exact cellular connection between no sugar and no seizures.

Roopra has previously explored how certain proteins known as "transcription factors" turn neuronal genes on or off. One transcription factor, NRSF is thought to control up to 1,800 genes in the brain, including many that are implicated in epilepsy.

NRSF ensures that neuronal genes switch "on" in the body's neurons, while remaining switched "off" in other regions where they normally play no role.

Roopra found that NRSF binds to another protein called CTBP. The finding "immediately raised alarm bells," Roopra said, because CTBP also binds to a free-floating molecule - NADH - that emerges when sugars break down in cells.

Roopra found that CTBP binds to either NRSF or NADH. In other words, a cell with a lot of glucose generates a lot of NADH, so CTBP is more likely to bind with the sugar by product than NRSF.

But without CTBP, NRSF most likely derails the normal function of certain neuronal genes - including those connected to epilepsy.

Scientists believe that NSRF also controls genes that potentially play a role in cancer. Roopra is planning future studies to test whether 2DG holds promise for combating breast cancer, or fast-spreading glioblastomas.

Roopra's findings are published in the journal Nature Neuroscience

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