Autistic behavior is curbed in French mouse study

MUNICH — A drug given to pregnant mice prevented autism-like behavior in their offspring, encouraging researchers they’re on the right track in testing the medicine in children with the disorder.

The study, published Tuesday in the journal Science, supports the rationale for using the medicine, called bumetanide, the lead researcher, Yehezkel Ben-Ari, said in a telephone interview. Bumetanide was marketed by Roche Holding under the brand name Bumex as a treatment for water retention in people with congestive heart failure and now is a generic drug.

“When we started our trial, it was a hypothesis, we had no evidence whatsoever,” Ben-Ari, a researcher at the Mediterranean Institute of Neurobiology in Marseille, France, said of the mid-stage trial in children. “This research doesn’t prove it, but it does validate our strategy.”

There are no drugs that cure autism or treat its core symptoms, according to the U.S. Centers for Disease Control and Prevention, so researchers and patient advocates are eager for any evidence of a promising treatment. Autism spectrum disorders are marked by problems in social interaction and communication and by restricted, repetitive and stereotyped patterns of behavior.

While the study looked at the effects of injecting pregnant rodents with bumetanide, treating pregnant women isn’t currently feasible because the condition can’t be diagnosed before birth, Ben-Ari said.

Ben-Ari’s research looked at the effects of bumetanide on a neurotransmitter in the brain that can alter autism-like behavior in offspring. The transmitter acts as a stimulant on neurons in the brain before birth, but has a braking effect afterward. In rodents either genetically or environmentally predisposed to develop an autism-like condition, the switch to an inhibitory effect doesn’t take place.

Giving bumetanide to pregnant rodents predisposed to autism shortly before they gave birth allowed the neurotransmitter to switch functions, leading to offspring that didn’t show autism- like behavior.

The abnormal neurotransmitter functions “may be a persistent and treatable feature” of autism spectrum disorders beyond infancy, Andrew Zimmerman of the University of Massachusetts Medical School and Susan Connors of Harvard Medical School said in an accompanying editorial.

More research is needed, Richard Mills, research director at Research Autism a U.K.-based autism charity, said in a telephone interview. “Using these interventions in mouse models is a long way from using them in humans,” said Mills, who wasn’t involved in Ben-Ari’s research.

A study of 8-year-olds in 2008 showed that one in 88 children were living with the condition in the U.S., according to the CDC.

Last year, Seaside Therapeutics and Roche said they would discontinue work on arbaclofen, a drug to treat autism spectrum disorders, after a mid-stage human trial didn’t show it to be effective.

Ben-Ari, who founded the company Neurochlore to commercialize his research, said he plans to have the results of the current trial by the end of 2014. A potential drug could be on the market in 2016 at the earliest, he said.

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