Researchers gain ground in efforts to fight parasite...( DALLAS May 26 2009 New findings by...),Health

DALLAS May 26, 2009 New findings by researchers UT Southwestern Medical Center are accelerating efforts to eradicate worm infections that afflict a third of the world's population.

The new findings, available online and in an upcoming issue of the Proceedings of the National Academy of Sciences, demonstrate that a biochemical system that controls development and reproduction of Caenorhabditis elegans, a common research worm, also provides the same function in several parasitic nematodes, including hookworm.

In these parasitic organisms, the activating molecule, called dafachronic acid, sends the necessary signals for the worms to mature from the stage in which they infect a host to the stage in which they start feeding on the host, which is what makes the host sick. In 2006 UT Southwestern scientists led by Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern and senior author of the new study in PNAS, had made the discovery in C elegans, a nematode about the size of a pinhead.

In the new study, the UT Southwestern researchers treated hookworm parasites pharmacologically at the infective larval stage with dafachronic acid, causing them to pass into the "feeding" larval stage outside a host, where they had no food supply and died. Treatment of other infectious species had similar effects.

"We essentially coaxed them to mature before a food source the host is available," Dr. Mangelsdorf said.

Many infectious nematode larva live in the soil, often in areas where proper sanitation is lacking. According to the World Health Organization, parasitic nematodes infect about 2 billion people worldwide and severely sicken some 300 million, at least 50 percent of whom are school-age children.

The results point to a promising therapeutic target for the infectious nematodes, said Dr. Mangelsdorf, an investigator with the Howard Hughes Medical Institute at UT Southwestern.

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