Autism may be caused by impairments within topoisomerases, a key group of enzymes whose integrity has significant bearing on brain development.

Researchers from the University of North Carolina’s School of Medicine made the discovery while studying topotecan – a chemotherapy drug designed to inhibit topoisomerase enzymes. In an experiment involving mouse models and human-derived nerve cells, the team noted that the drug tended to interfere with particularly “long” genes – a signature property of autism linked genes. The finding may indicate an environmental factor behind the condition, and shed new light on its genetic roots.

"Our study shows the magnitude of what can happen if topoisomerases are impaired," senior study author Mark Zylka said in a press release. "Inhibiting these enzymes has the potential to profoundly affect neurodevelopment – perhaps even more so than having a mutation in any one of the genes that have been linked to autism."

Complications within this group of enzymes could thus exacerbate significantly the developmental impairments caused by autism’s extremely long genes.

"A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development,” Zylka explained. "It could ultimately explain the biological mechanisms behind a large number of autism cases."

Future research will attempt to catalogue other compounds that have similar inhibitive effects on genes. If such environmental agents augment the developmental complications of autism-linked genes, reduced public exposure may have significant bearing on the number of Autism Spectrum Disorder (ASD) cases.

"If there are additional compounds like this in the environment, then it becomes important to identify them," said Zylka. "That's really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects – so that pregnant women can avoid being exposed to these compounds."

According to the Centers for Disease Control and Prevention (CDC), ASD occurs in about 1.1 percent of children born in the U.S. The condition affects brain development, and usually restricts the ability to modulate along social contexts and adapt to new situations. To learn more about the disorder, visit the advocacy and awareness group Autism Speaks.

Source: Ian F. King, Chandri N. Yandava, Angela M. Mabb, Jack S. Hsiao, Hsien-Sung Huang, Brandon L. Pearson, J. Mauro Calabrese, Joshua Starmer, Joel S. Parker, Terry Magnuson, Stormy J. Chamberlain, Benjamin D. Philpot, Mark J. Zylka.Topoisomerases facilitate transcription of long genes linked to autism. Nature, 2013

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