Experimental drug for autism works effectively in laboratory mice: Study

By Dr. Ananya Mandal, MDApr 26 2012

A new experimental drug has shown promise in autism symptoms in mice. Researchers from the National Institutes of Mental Health and Pfizer reported Wednesday that an experimental compound, called GRN-529, increased social interactions and lessened repetitive self-grooming behavior in a strain of mice bred to display autism-like behaviors.

Before treatment one of the mice was interested only in repeatedly cleaning its coat of fur. After getting the drug, it went to an attached cage to try to engage with a new mouse it had never encountered before.

The study, published in the journal Science Translational Medicine, is one of several to test a class of drugs that inhibit a cell receptor called mGluR5, that’s known to play a role in Fragile X, an autistic-like syndrome. Clinical trials to test these drugs on Fragile X patients are already underway. 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.

“Our findings suggest a strategy for developing a single treatment that could target multiple diagnostic symptoms,” Jacqueline Crawley, a researcher at the mental health institute, said in a statement. “Many cases of autism are caused by mutations 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.”

“Together, the new and previous findings suggest that clinical trials should be initiated to test the effects of mGluR5 inhibitors in autism patients,” wrote Baltazar Gomez-Mancilla, a researcher for the drug company Novartis, in a paper that accompanied the study.

But whether the agent would work in older children and adults with autism remains questionable at best. It could be, added Gomez-Mancilla, that “the limited plasticity of the adult brain mandates intervention at earlier ages, ideally at the time of diagnosis.”

At present there is no cure for the condition. Autism spectrum disorder is thought to affect around 1% of children. It ranges from mild to severe and symptoms include social problems, delayed language and repetitive movements such as hand tapping. Autism is mainly treated with specialist education, speech and behavioural therapies.

Crawley said, “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.”

Uta Frith, a professor of cognitive development at University College London, said, “Processes at the level of the synapse have long been suspected in the origin of autism. However, it will be a long time until these findings can be translated for human patients. Tampering with the synapse may well result in undesirable side effects. Despite hopeful signs for a future drug treatment of at least some autistic behaviours, it would be sad if too much pressure was now put on researchers to rush into applications.”

Richard Mills, the director of research at the National Autistic Society, said, “The NAS welcomes all research that improves our understanding of the neurobiology of autism. Research using animal models is important but it is not always easily translated into our understanding of autism in humans.”

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.

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.