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Commonplace Sugar Controls Seizures

Commonplace Sugar Controls Seizures
This sugar has been in clinical use for decades, but now it is finding new uses, a potential cure for epilepsy.

2-deoxy-glucose, or 2DG, has long been used in radio labeling, medical scanning and cancer imaging studies in humans. But now, scientists at the University of Wisconsin-Madison have found the substance also blocks the onset of epileptic seizures in laboratory rats.

Published in the journal Nature Neuroscience, the findings have potentially huge implications for up to half of all epileptic patients who currently have no access to therapy, says senior author Avtar Roopra, a UW-Madison assistant professor of neurology.

"We pumped the rats full [of 2DG] and still saw no side effects," says Roopra, who estimates that the compound may be available for human use within five years. "I see 2DG as an epilepsy management therapy much like insulin is used to treat diabetes."

"All the available epilepsy therapys have focused on suppressing seizures," says co-author and renowned epilepsy expert Tom Sutula, a UW-Madison professor of neurology. "There has been hope that [new drugs] will not only suppress seizures, but modify their consequences. [2DG] appears to be a novel therapy that offers great promise to achieve that vision."

About 1 percent of the world's population suffers from epilepsy, a neurological condition that makes people susceptible to seizures. Researchers think that seizures, of which there are a number of kinds, occur due to sudden changes in how brain cells send electrical signals to each other. In about 30 to 50 percent of epilepsy patients, available therapys - including the removal of parts of the brain's temporal lobe - are largely ineffective.

2DG is essentially a more palatable version of the "ketogenic," or sugar-free, diets that some scientists have long recommended to epilepsy patients. Indeed, the notion of a sugar-free diet actually stretches back thousands of years to Biblical times, when healers sometimes prescribed starvation as a potent way to fend off seizures.

UW-Madison scientists first began to investigate the role of sugar in controlling seizures after early experiments showed that children on sugar-free diets can rapidly experience seizures when they consume even a small dose of carbohydrates, such as a cookie or a little piece of bread.

But ketogenic regimens can be a miserable experience. "The kids can't eat any sugar at all. Imagine no bread or Christmas cake," says Roopra. But 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.

Though ketogenic diets seem to work in a number of epilepsy patients in whom existing therapys have been unsuccessful, researchers have struggled to understand the exact cellular correlation between no sugar and no seizures. The UW-Madison work for the first time clears up some of that mystery.

Roopra has long explored how certain proteins known as "transcription factors" turn neuronal genes on or off. He has been especially intrigued by one transcription factor known as NRSF, which is thought to control up to 1,800 genes in the brain, including a number of that are implicated in epilepsy. Like an electrical motherboard, 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 observed that NRSF binds to another protein called CTBP. The finding "immediately raised alarm bells," Roopra says, because CTBP also binds to a free-floating molecule - NADH - that emerges when sugars break down in cells. To his surprise, Roopra observed 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 byproduct than NRSF. But without CTBP, NRSF most likely derails the normal function of certain neuronal genes - including those connected to epilepsy.

Researchers think 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.

The UW-Madison team has patented 2DG for its use against epilepsy in collaboration with the Wisconsin Alumni Research Foundation, UW-Madison's technology transfer arm.


Posted by: Daniel    Source




Did you know?
This sugar has been in clinical use for decades, but now it is finding new uses, a potential cure for epilepsy. 2-deoxy-glucose, or 2DG, has long been used in radio labeling, medical scanning and cancer imaging studies in humans. But now, scientists at the University of Wisconsin-Madison have found the substance also blocks the onset of epileptic seizures in laboratory rats.

Medicineworld.org: Commonplace Sugar Controls Seizures

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