April 6, 2011

Parasite May Help Crohn’s Disease Research

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Researchers in Cornell’s College of Veterinary Medicine are working toward a cure for Crohn’s disease, of which the causes are still unknown.

The work comes after a breakthrough in 2009 when Prof. Eric Denkers, immunology, and a research associate, Charlotte Egan, discovered that mice infected with the parasite Taxoplasma gondii presented symptoms similar to those found in human patients with Crohn’s disease. Denkers’ lab began using Toxoplasma-infected mice as an animal model for Crohn’s.

Crohn’s disease, which is characterized by inflammation of the small intestine, is triggered by an “abnormally robust response to normal bacteria in the intestinal system,” according to Thomas Ullman MD ’92, director of the Center for Inflammatory Bowel Disease at The Mount Sinai School of Medicine.

In response to harmful bacteria, the immune system recruits cells — known as intraepithelial lymphocites — to the infection site, and an excess accumulation of these cells can cause inflammation in the small intestine, according to Egan.

“We see the same thing in mice that are infected with Toxoplasma,” Denkers said. “So what we think is that this parasite causes the same disregulated response to gut bacteria.”

Still, the researchers say their findings are unconfirmed.

“The Crohn’s therapy graveyard is full of things that looked great in the lab or in animal testing,” Ullman said. “But that’s not to discourage anyone from doing research in Crohn’s disease. Denkers’ work may turn out to be a great benefit to Crohn’s patients.”

Denkers and Egan compared mice whose intestines were inflamed by Toxoplasma gondii to a strain of mice resistant to the disease.

“We found this profound increase of intraepithelial lymphocites in the diseased animal, but not in the resistant animal,” Egan said. “So what we’ve been doing is isolating these cells and trying to better understand their function.”

Denkers and his colleagues are using the experiment to develop possible treatments to Crohn’s disease.

“The resistant mice are defective in the recruitment of these cells to the infection site,” Denkers said. “Maybe if we could block the recruitment of these damaging cells to inflammatory lesions in humans, we could be able to treat disease somewhere down the road.”

The experiment is in the early stages of testing and the results will need to be confirmed by other labs, according to Denkers, who added that there has been no response yet from the medical community.

While Denkers’ study shows that Toxoplasma gondii in mice is a successful model of human Crohn’s disease for research purposes, it does not indicate that the parasite is responsible for the disease in humans.

“There is really no evidence that Toxoplasma in humans is a cause of Crohn’s disease,” Denkers said.  “We don’t really know what the trigger is in humans.”

According to Ullman, it can take a while for research such as Denkers’ to make the leap from “pre-clinical bench work” to “practical, patient-oriented applications.”

Denkers and Egan published their discovery in Mucosal Immunology, and their research was reviewed in the Journal of Biomedicine and Biotechnology. An impending paper on the project is currently undergoing revision.

Original Author: Rebecca Harris