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Drug shows early promise in treating seizures
Date:11/17/2013

A study out today in the journal Nature Medicine suggests a potential new treatment for the seizures that often plague children with genetic metabolic disorders and individuals undergoing liver failure. The discovery hinges on a new understanding of the complex molecular chain reaction that occurs when the brain is exposed to too much ammonia.

The study shows that elevated levels of ammonia in the blood overwhelm the brains defenses, ultimately causing nerve cells to become overexcited. The researchers have also discovered that bumetanide a diuretic drug used to treat high blood pressure can restore normal electrical activity in the brains of mice with the condition and prevent seizures.

"Ammonia is a ubiquitous waste product of regular protein metabolism, but it can accumulate in toxic levels in individuals with metabolic disorders," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article. "It appears that the key to preventing the debilitating neurological effects of ammonia toxicity is to correct a molecular malfunction which causes nerve cells in the brain to become chemically unbalanced."

In healthy people, ammonia is processed in the liver, converted to urea, and expelled from the body in urine. Because it is a gas, ammonia can slip through the blood-brain-barrier and make its way into brain tissue. Under normal circumstances, the brains housekeeping cells called astrocytes sweep up this unwanted ammonia and convert it into a compound called glutamine which can be more easily expelled from the brain.

However, individuals with certain genetic metabolic disorders and people with impaired liver function because of chronic hepatitis, alcoholism, acetaminophen overdose, and other toxic liver conditions cannot remove ammonia from their bodies quickly enough. The result is a larger than normal concentration
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Contact: Mark Michaud
mark_michaud@urmc.rochester.edu
585-273-4790
University of Rochester Medical Center
Source:Eurekalert

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