Potential Cause of Autism Identified

Problems with a group of enzymes known as topoisomerases can have significant repercussions on the genetic machinery behind brain development and perhaps lead to autism spectrum disorder (ASD), a new study shows.

Topoisomerases are found in all human cells where they are tasked with untangling DNA that becomes overwound and, as the new study shows, can have profound implications when impaired.

Led by researchers from the University of North Carolina School of Medicine, the study took root when Mark Zylka, associate professor the Neuroscience Center and the Department of Cell Biology and Physiology, and his colleagues were studying topotecan, a topoisomerase-inhibiting drug used in chemotherapy.

They were investigating the drug's effects in mouse and human-derived nerve cells when they noticed the drug interfered with the functioning of especially long genes. Knowing that many autism-linked genes are extremely long, the scientists determined there may be a connection.

"That's when we had the 'Eureka moment,'" said Zylka. "We realized that a lot of the genes that were suppressed were incredibly long autism genes."

Sure enough, of more than 300 genes linked to autism, topotecan suppressed nearly 50 of them.

According to the study's press release, "Suppressing that many genes across the board -- even to a small extent -- means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene."

The study, Zylka explains, could have important implications not only for ASD detection, but prevention as well.

"This could point to an environmental component to autism," said Zylka. "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. "

Furthermore, the researchers believe the findings could offer an explanation as to why some people with mutations in topoisomerases develop autism while others develop neurodevelopmental disorders.