Discovery at UNC points to possible environmental cause of autism

Posted: Published on October 22nd, 2013

This post was added by Dr Simmons

Researchers at UNC School of Medicine have discovered a potential environmental cause of autism in a type of chemotherapy drug, and they are beginning to investigate the effects of other non-chemo drugs that work by a similar mechanism.

Professors Mark Zylka and Benjamin Philpot made the discovery while studying a drug thats effective against cancer, but also shows potential as a treatment for a genetic disease called Angelman syndrome. In the process, they made some new observations that seem to point to a cause of autism. Thats science, says Zylka. Youre trying to do something and you find something else.

The duo, along with colleagues at UNC Chapel Hill and the University of Connecticut, published their results in the journal Nature on Aug. 28.

On Sept. 30, the National Institutes of Health awarded Zylka a Pioneer Award to continue the autism work. Only about a dozen researchers receive the annual award, which provides up to $2.5 million over five years. According to the NIH website, the award supports researchers of exceptional creativity, who propose pioneering and possibly transforming approaches to major challenges in biomedical and behavioral research.

Zylka and Philpot are both associate professors in the department of cell biology and physiology at UNCs School of Medicine, but they might never have worked together if it werent for the proximity of their labs. Zylka studies the neurology of pain; Philpot studies Angelman syndrome, a genetic disorder that is sometimes misdiagnosed as autism or cerebral palsy. The two often discussed their work when they saw each other in the halls or at lunch.

They started collaborating on projects related to the perception of pain in people with Angelman syndrome. Recently, they broadened their collaboration by pooling funds to purchase a genome sequencing machine, which they used to investigate how the cancer drug topotecan affects specific genes. This project grew out of work Philpot did a couple of years ago that showed topotecan might be useful in treating Angelman syndrome.

As a cancer drug, topotecan works by gumming up cell division to halt tumor growth. It does this by inhibiting enzymes called topoisomerases, which keep DNA from becoming knotted up.

In our cells, DNA is typically tightly wound in packages for efficient storage. But DNA must be unwound during two crucial processes: cell division and gene expression. Topoisomerases make this unwinding possible. Zylka calls the enzymes scissors and glue, saying, They cut the DNA, uncoil it, and stick it back together very, very fast.

In the case of Angelman syndrome, Philpot was interested not in cell division but in gene expression the process by which genes do their biological jobs, whether specifying eye color or telling a cell to become a neuron.

The eureka moment

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Discovery at UNC points to possible environmental cause of autism

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