From: Reuters
Published May 7, 2008 06:08 PM

Weight-loss drugs may harm developing brain: study

By Julie Steenhuysen

CHICAGO (Reuters) - A drug from a new class of weight-loss treatments disrupted wiring needed for brain development in young mice, U.S. researchers said on Wednesday, raising concerns about using such medications in children.

Mark Bear and colleagues at the Massachusetts Institute of Technology studied the effects of a chemical that suppresses appetite by blocking cannabinoid receptors in the brain, the same brain mechanisms that make people hungry when they smoke marijuana.

"I think that the cautionary note is that these mechanisms play an important role in ... brain development," said Bear, whose study appears in the journal Neuron.

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Sanofi-Aventis' weight-loss pill rimonabant, also known as Zimulti and sold under the brand name Acomplia in Europe, is the first in this new class of drugs. A U.S. expert panel rejected it last June because of fears it might trigger suicidal thoughts.

Other drugmakers, including Merck & Co Inc, are working on similar drugs.

Bear's team at MIT was hoping to gain insight into how the brain adapts and rewires itself through learned experiences. This so-called plasticity is central to the development of neurons in the brain of children and young animals.

Bear said these cannabinoid receptors are known to regulate signals between neurons, and his team wanted to see if they would have an effect on plasticity in these young mice.

They were specifically testing learning in the visual cortex of the mouse, a part of the brain that processes information gathered from what they see.

ADAPTING TO CHANGE

Their experiments tested how well the animals adapted if one eye was closed.

The researchers did not use rimonabant in the study. Instead, they used a chemical analog or copy -- in this case a drug available for laboratory use known as AM 251.

When they gave the mice AM 251 to block their cannabinoid receptors, the animals still behaved as if both eyes were open. This suggested the visual cortex was not adapting as it should.

"Our finding of a profound disruption of cortical plasticity in juvenile mice treated with AM 251 suggests caution is advised in the use of such compounds in children," the researchers wrote.

Bear said the finding is similar to the situation with many drugs.

"You have to weigh the benefits against the risks. If the benefit is related more to vanity than morbidity, I don't think the risks are tolerable," he said.

Sanofi-Aventis spokeswoman Julissa Viana said rimonabant is not approved for use in children.

"At this point in time it is approved for use in adults who are overweight and obese with cardiovascular risk factors," she said. "We don't encourage its use in children and it has not been studied nor is it indicated for use in children."

The finding is the latest blow for rimonabant, which once was predicted to be a multibillion-dollar seller.

A study last month of the drug in obese heart patients found more than 40 percent of patients who took the drug developed psychiatric problems.

But last month the drugmaker Sanofi said it still believes Acomplia can be a winner and reiterated plans to submit the drug worldwide as a treatment for type 2 diabetes in 2009.

(Editing by Maggie Fox and Xavier Briand)

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