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
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
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
"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
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
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."
Still, he added, this line of research is very promising.
"There are now multiple clinical trials underway of mGluR5 antagonists in individuals with Fragile X syndrome," Veenstra-VanderWeele said. "Many of us hope that these medications will help not only those who have autism spectrum disorder due to Fragile X syndrome but some people within the larger group of those with [autism spectrum disorder] not due to a well-understood cause. Of course, that hope hasn't yet been tested."
He said this new study is "an exciting hint that the mGluR5
hypothesis may extend outside of Fragile X Syndrome." If that's
true, he said, it could potentially point to a role for this
receptor in the biology underlying repetitive behavior and social
Experts noted that many cases of autism likely involve more than
excessive glutamate signaling. Even in the mice, GRN-529 helped
with certain symptoms, but not with all. For instance, the mice
still didn't communicating normally.
Pfizer's Smith said GRN-529 is not being considered for clinical
trials. Pfizer declined to give any more details about future
research into GRN-529 or other glutamate-inhibiting drugs.
National Institutes of Health has more on autism.
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