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Study Sheds Light on Treatment Targets for Autism

Researchers have identified a link between the overproduction of certain brain proteins and symptoms of autism spectrum disorder (ASD). They also reversed autism-like behaviors in mice by stopping the overproduction of these proteins. They did so using an experimental compound and by inducing specific changes in brain gene expression. 

The findings stimulate interest in the development of similar compounds to treat autism, says Autism Speaks Senior Director of Discovery Neuroscience Daniel Smith, Ph.D. “The study advances our understanding of how certain brain signaling pathways underlying ASD may cause autism’s core behavioral symptoms,” Dr. Smith adds. Autism Speaks partly funded the study, published in this week’s issue of Nature.  

“Even though autism is a neurodevelopmental disease, we were able to correct autism-associated behaviors in adult mice,” says lead author Christos Gkogkas, Ph.D. Dr. Gkogkas is a postdoctoral fellow in the department of biochemistry at McGill University, in Montreal.

The study focused on brain proteins called neuroligins. “Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain,” says study co-author Nahum Sonenberg, Ph.D., of McGill University and its Goodman Cancer Research Centre. The researchers found that abnormal production of neuroligins increases synaptic activity between neurons. This causes an imbalance between excitation and inhibition in brain cells. Previous research has suggested that such imbalances are behind at least some of autism’s core symptoms.  

Dr. Sonenberg’s lab normally studies abnormal protein synthesis in cancer. While working with mice genetically altered to be susceptible to cancer, they discovered cell mechanisms similar to those associated with autism. Their mouse model has a gene deletion that increases the production of neuroligins. This, in turn, produced autism-like behaviors in the mice. They had impaired social interaction and communication and increased repetitive behaviors.

The McGill scientists tried to reverse the autism-like behaviors. “The first strategy was to use compounds developed for treating cancer,” says Dr. Gkogkas. “We were able to reduce protein synthesis and reverse autism-like symptoms in adult mice.”

In a second strategy, they used a technology similar to gene therapy. They treated the mice with viruses engineered to block the production of neuroligins. Again, they reversed the behavioral symptoms.

“Abnormal protein synthesis may be a mechanism explaining many different genetic defects linked to autism,” says Dr. Gkogkas.

“The advance from this study is that it reveals a specific biochemical relationship inside neurons that causes brain and behavior changes associated with autism,” Dr. Smith adds. “This is a very elegant and scientifically rigorous study that confirms and expands a growing list of targets for ASD medicines.”

Autism Speaks is currently funding a variety of studies aimed at understanding and normalizing the function of brain neurons in autism. You can explore these and other funded research using this website’s Grant Search.

Reported by Autism Speaks science writer Laurie Tarkan