Hope for New Schizophrenia Drugs

(December 6, 2007) -- A target in the brain has been found that will enable doctors to develop new drugs to treat schizophrenia, the most common form of psychosis.

The term schizophrenia probably covers a wide range of problems that disrupt thinking. Now another step towards understanding one of the underlying causes has been taken that has already revealed two types of candidate drug that could, in theory, treat the mental disorder.

In a study published today in the journal Science, Prof Laura Dugan, Dr Margarita Behrens of the University of California, San Diego, and colleagues have determined what may be one of the initial changes in brain chemistry that leads to schizophrenia, showing that it is collateral damage caused by an enzyme that usually helps protect the body against infection.

The team used an established way to mimic schizophrenia in mice by using the drug ketamine. Also known as the street drug Special-K, ketamine, was developed to be an anesthaetic for surgery but it is also used as a recreational drug for its hallucinatory effects.

When the researchers injected mice with ketamine, they found that the drug triggered a rapid, strong increase of a highly reactive and toxic chemical called "superoxide", made by an inflammatory enzyme, and this superoxide caused the loss of a specific subset of cells in a region of the brain called the prefrontal cortex.

The scientists then determined that using a drug called a Nox inhibitor, or one that destroys superoxide, to target the enzyme or its product they could prevent these effects, suggesting that using related drugs or antioxidants to mop up the superoxide might provide future treatments for drug-induced psychosis or schizophrenia.

The find was unexpected because the enzyme responsible, NADPH oxidase is normally found in white blood cells circulating outside the brain, where it helps kill bacterial and fungal infections by producing superoxide.

"Because of NADPH oxidase's protective role in fighting infection, it was very surprising to find that the complex wears a second hat - it is also critical for modulating signaling in the brain," said Dr Behrens.

"Our findings suggest that compounds that inhibit NADPH oxidase in the brain, without totally blocking its protective function of killing bacteria, could provide future therapies for schizophrenia or other diseases in humans that exhibit similar changes in neural circuitry."

Schizophrenia is a mental disorder that affects around 1 in every 100 people. It affects men and women equally and seems to be more common in city areas and in some minority ethnic groups. It is rare before the age of 15, but can start at any time after, most often between the ages of 15 and 35. ends

By Roger Highfield
Source: Telegraph.co.uk

Last updated: 12/07

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