Autism Linked to Genetic Mutation – and Researchers Say They Can Undo It

The genetic roots of autism have been investigated for more than a decade, as DNA sequencing has continued to improve. A new, early study points to a particular mutation in mice causing autistic-like behavior, adding to a list of potential causes.

But the scientists also say they’ve tracked the chemical trail from the genetic anomaly – and they have found a way to reverse the entire process, adding a new wrinkle to the research.

“We observed a robust and long-lasting rescue of the social interaction deficits and repetitive behavior (in the mice),” said Zhen Yan, professor of the Department of Physiology and Biophysics at the University Buffalo (SUNY), who led the study. “Our results suggest a promising therapeutic strategy for treating autism.”

The paper, published today in Cell Reports, focused on the role of Shank3, a gene that has been identified in autism in prior studies.

Yan and her colleagues found a Shank3 mutation that causes disrupted communication between neurons, and social deficits in the laboratory mice, they said.

The affected mice had drastically reduced interest in interacting with others. They would also repetitively groom themselves, the scientists found.

Because of the Shank3 mutation, the mice were not able to regulate actin filaments, which are crucial to carrying information in the brain’s prefrontal cortex, where “high-level” executive functions are made, the research found.

However, by chemically treating the deficits and other anomalies, the mice were “rescued” from the autism-like behaviors, the scientists discovered.

“Thus, targeting actin regulators provides a strategy for autism treatment,” Yan wrote, adding that it suggests potential pharmaceutical targets for treatment.

Autism’s causation factors, which are only becoming better understood in last two decades, remain a mystery. Since the disorder spectrum shows such diversity of symptoms and behaviors, even diagnosis is a challenge in the early stages of development.

However, experts at the National Institutes of Health and elsewhere continue to believe that genetics and environment play some role in causing autism.

The University at Buffalo study is not the first to focus on genetic factors – or even the Shank3 gene. Last year, a study of nine children conducted by the Seaver Autism Center in New York City found that short-term treatment of Shank3-affected autistic children with Insulin-like Growth Factor, or IGF, improved social interaction and reduced repetitive behaviors.

The Autism Genome Project has been searching for a wide swath of genetic causation of spectrum disorders since 2004. According to the advocacy group Autism Speaks, clinicians can now identify the genetic basis of some 10 to 20 percent of autism cases.

But the efforts have appeared to ramp up since DNA analysis has become more widely available, and cheaper. In March, a team at Johns Hopkins University studied the rare tendency of some autism disorders to run among the females in families. Through genetic sequencing of those families, the scientists identified the CTNND2 gene as a driver of certain autism disorders, as published in the journal Nature.