Agent reduces autism-like behaviors in mice

April 25, 2012
A mouse pays a social visit to a novel animal. Credit: MuYang, Ph.D., and Jacqueline Crawley, Ph.D., NIMH Laboratory of Behavioral Neuroscience

National Institutes of Health researchers have reversed behaviors in mice resembling two of the three core symptoms of autism spectrum disorders (ASD). An experimental compound, called GRN-529, increased social interactions and lessened repetitive self-grooming behavior in a strain of mice that normally display such autism-like behaviors, the researchers say.

GRN-529 is a member of a class of agents that inhibit activity of a subtype of receptor protein on for the , which are being tested in patients with an autism-related syndrome. Although findings often don't translate to humans, the fact that these compounds are already in clinical trials for an overlapping condition strengthens the case for relevance, according to the researchers.

"Our findings suggest a strategy for developing a single treatment that could target multiple diagnostic symptoms," explained Jacqueline Crawley, Ph.D., of the NIH's National Institute of Mental Health (NIMH). "Many cases of autism are caused by in genes that control an ongoing process – the formation and maturation of synapses, the connections between neurons. If defects in these connections are not hard-wired, the core symptoms of autism may be treatable with medications."

Crawley, Jill Silverman, Ph.D., and colleagues at NIMH and Pfizer Worldwide Research and Development, Groton, CT, report on their discovery April 25th, 2012 in the journal Science Translational Medicine.

The video will load shortly.
The video shows an untreated BTBR mouse absorbed in repetitive self-grooming. Credit: MuYang, Ph.D., Adam Katz, and Jacqueline Crawley, Ph.D., NIMH Laboratory of Behavioral Neuroscience

"These new results in mice support NIMH-funded research in humans to create treatments for the core symptoms of autism," said NIMH director Thomas R. Insel, M.D. "While autism has been often considered only as a disability in need of rehabilitation, we can now address autism as a disorder responding to biomedical treatments."

Crawley's team followed-up on clues from earlier findings hinting that inhibitors of the receptor, called mGluR5, might reduce ASD symptoms. This class of agents – compounds similar to GRN-529, used in the mouse study – are in for patients with the most common form of inherited intellectual and developmental disabilities, Fragile X syndrome, about one third of whom also meet criteria for ASDs.

To test their hunch, the researchers examined effects of GRN-529 in a naturally occurring inbred strain of mice that normally display autism-relevant behaviors. Like children with ASDs, these BTBR mice interact and communicate relatively less with each other and engage in repetitive behaviors – most typically, spending an inordinate amount of time grooming themselves.

Crawley's team found that BTBR mice injected with GRN-529 showed reduced levels of repetitive self-grooming and spent more time around – and sniffing nose-to-nose with – a strange mouse.

Moreover, GRN-529 almost completely stopped repetitive jumping in another strain of mice.

"These inbred strains of mice are similar, behaviorally, to individuals with autism for whom the responsible genetic factors are unknown, which accounts for about three fourths of people with the disorders," noted Crawley. "Given the high costs – monetary and emotional – to families, schools, and health care systems, we are hopeful that this line of studies may help meet the need for medications that treat core symptoms."

Explore further: Repetitive behaviors in adults with Autism Spectrum disorders significantly lessen with antidepressant treatment

More information: Silverman JL, Smith DG, Rizzo SJS, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley, JN. Negative allosteric modulation of the MGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. April 25, 2012, Science Translational Medicine.

Related Stories

Repetitive behaviors in adults with Autism Spectrum disorders significantly lessen with antidepressant treatment

December 5, 2011
(Medical Xpress) -- Restricted, repetitive behavior, such as compulsive arranging and rigid adherence to routines, is a defining symptom of autism spectrum disorders.

Recommended for you

Signaling pathway may be key to why autism is more common in boys

October 17, 2017
Researchers aiming to understand why autism spectrum disorders (ASD) are more common in boys have discovered differences in a brain signaling pathway involved in reward learning and motivation that make male mice more vulnerable ...

Whole genome sequencing identifies new genetic signature for autism

October 12, 2017
Autism has genetic roots, but most cases can't be explained by current genetic tests.

Mum's immune response could trigger social deficits for kids with autism

October 10, 2017
The retrospective cohort study of 220 Australian children, conducted between 2011-2014, indicates that a "an immune-mediated subtype" of autism driven by the body's inflammatory and immunological systems may be pivotal, according ...

Largest study to date reveals gender-specific risk of autism occurrence among siblings

September 25, 2017
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Faulty cell signaling derails cerebral cortex development, could it lead to autism?

September 20, 2017
As the embryonic brain develops, an incredibly complex cascade of cellular events occur, starting with progenitors - the originating cells that generate neurons and spur proper cortex development. If this cascade malfunctions ...

Predicting atypical development in infants at high risk for autism?

September 12, 2017
New research from the Sackler Institute for Developmental Psychobiology at Columbia University Medical Center (CUMC) identifies a potential biomarker that predicts atypical development in 1- to 2-month-old infants at high ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.