Experimental Drug Eases Autistic Behaviors in Mice

Whether it would work on humans is still unknown, researchers say

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By Jenifer Goodwin
HealthDay Reporter

WEDNESDAY, April 25 (HealthDay News) -- An experimental drug reduced two signature characteristics of autism -- repetitive behavior and abnormal social interactions -- in laboratory mice, new research finds.

The drug, GRN-529, targets glutamate, a major neurotransmitter found throughout the brain that's involved with activating neurons, or brain cells. Researchers believe the compound works through a specific glutamate receptor (mGluR5) and decreases glutamate activity.

Researchers bred mice to have the hallmarks of autism -- including unusual social interactions, impaired communication and repetitive self-grooming -- and injected them with GRN-529.

Almost immediately, the mice showed fewer repetitive behaviors and more normal social interactions, although their communication was still not typical.

"These findings offer encouragement that research focused on developing medicines for core symptoms of autism are gaining momentum," said study co-author Robert Ring, vice president for translational research for Autism Speaks, an autism research and advocacy organization.

Experts caution, however, that although studies in animals can be useful, the results of animal studies often don't hold up in humans.

The study is in the April 25 issue of the journal Science Translational Medicine.

Autism is a neurodevelopmental disorder characterized by problems with social interaction, verbal and nonverbal communication, and restricted interests and behaviors. An estimated one in 88 U.S. children has autism, according to the U.S. Centers for Disease Control and Prevention.

Until recently, experts believed that the core symptoms of neurodevelopmental disorders such as autism and Fragile X syndrome, a genetic disorder that shares many of the same symptoms as autism, couldn't be treated well with medications, because the underlying abnormalities were "hardwired" into the brain during fetal development, according to background information in the study.

But now that dogma is being challenged, said study co-author Daniel Smith, a senior research scientist at Pfizer Worldwide Research and Development.

Studies have suggested that some genes involved with autism play a role in the formation of brain synapses throughout childhood, and even into adulthood. That has led researchers to hunt for compounds that could alter how those genes function.

In Fragile X, for example, research suggests that excessive glutamate signaling may underlie the condition, and clinical trials are already underway by Novartis, Seaside Therapeutics and Roche to test other compounds that inhibit glutamate activity, Ring said.

"Because Fragile X symptoms overlap with autism symptoms, we hypothesized this same mechanism might affect autism patients from populations other than Fragile X," Smith said.

In an accompanying journal editorial, Baltazar Gomez-Mancilla, executive director of translational medicine neuroscience at Novartis, wrote that GRN-529 reduced repetitive behavior and partially reversed lack of sociability in a mouse model of autism.

And yet this is only "early stage, preclinical research" that will help advance the understanding of molecular mechanisms involving the mGluR5 receptor and generate more avenues for research, Gomez-Mancilla said.

"It is too early to speculate as to whether or not autism spectrum disorders can be reversed by small molecules," Gomez-Mancilla said.

Gomez-Mancilla wrote that this trial and previous work on mGluR5 inhibitors support further clinical trials. If the trials show the drugs are effective, a major question would be whether children should receive the drugs when diagnosed or if adults would also benefit.

Dr. Jeremy Veenstra-VanderWeele, an assistant professor of psychiatry, pediatrics and pharmacology at Vanderbilt University in Nashville, Tenn., said other considerations exist. Mice don't have to learn much throughout their lifetimes to engage in normal mouse activities, whereas "humans need to learn a ton in order to function typically in a social setting," he said. "We don't know how well interventions that normalize social interest at a defined point in time will impact actual social function."