Jew World Order

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.”

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 interaction.

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.

More information

The U.S.
National Institutes of Health has more on autism.