A Tale of the Tapeworm: Parasite ploy suggests drug-delivery tactic

For the tapeworm Hymenolepis diminuta, heaven is a rat’s intestines. A single, nearly foot-long parasite can live there for years. It’s no wonder then that the tapeworm has developed means for keeping itself lodged within an often undulating mammalian gut.

Scientists at the University of Wisconsin–Madison have now identified one of the parasite’s tools: A chemical that it secretes slows intestinal pulsations.

Known as cyclic guanosine monophosphate, or cGMP, the chemical may also play a role in the normal control of any mammal’s digestive system. Given that possibility, the Wisconsin investigators have filed for a patent on the idea of adding cGMP to drugs in order to lengthen the amount of time they spend in the gut and thus increase how much medicine a person absorbs.

John Oaks and his colleagues in Madison have long studied how tapeworms such as H. diminuta thrive inside a mammal’s intestinal tract. “The tapeworm knows when the animal is going to feed and migrates from one end of the bowel to where the food is coming out of the stomach,” Oaks says. “It comes back down the small intestine as food is digested.”

Between meals, a mammal’s intestinal muscles normally contract rhythmically to sweep out bacteria and waste. This action poses a danger to tapeworms. About a decade ago, however, Oaks’ team discovered that the parasite mounts a counterattack by somehow slowing down this sweeping wave of intestinal motility.

Recently, the researchers found that tapeworm secretions by themselves could achieve the same result. The key chemical in those secretions turned out to be cGMP, says Oaks, and that was a surprise.

That chemical typically operates in cells, where it participates in conveying signals from the inside of a cell’s membrane to other parts of the cell. The new research suggests that cGMP also serves as a signal outside of cells. The investigators are now racing to identify cGMP’s receptor, a molecular binding site that they presume resides somewhere on the surfaces of intestinal cells.

Oaks and his colleagues speculate that animals use cGMP to regulate natural muscle contractions within the intestinal tract. “It’s probably an in-place system in every animal,” says Oaks. “The tapeworm was adaptive enough to take advantage of this to provide for its own survival.”

“This could tell us a lot about the regulation of intestinal function,” adds Norman W. Weisbrodt of the University of Texas in Houston, who studies gastrointestinal motility.

Like the parasite, Oaks and his colleagues hope to take advantage of cGMP. They’ve already shown that an easily tracked molecule takes longer to pass through the intestines when rodents are infected with tapeworms. They’re now testing whether drugs combined with cGMP also move more slowly and, if so, whether extra travel time enhances absorption of medicine.

Oaks notes that for some pills, only 1 percent of a drug is taken up into the bloodstream. The rest is excreted into the sewage system–or in the case of medicated livestock, into the environment. Scientists are just beginning to explore the impact of such drug waste in polluting water and soil (SN: 4/01/00, p. 212: More Waters Test Positive for Drugs).

With cGMP, says Oaks, “we could perhaps lower the amount of drug necessary for treating an individual and minimize environmental contamination.”

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