Tapeworm's trick could make drugs more effective

Madison, Wis. ­

To survive and thrive in a decidedly hostile environment, the lowly tapeworm uses a chemical trick to evade the propulsive nature of its intestinal home, say scientists at the University of Wisconsin-Madison (UW).

Capitalizing on that tapeworm chemistry, scientists at UW believe theymay have found a way to slow the transit of drugs through the intestine,making them more effective in their delivery and holding out the promisenot only of more effective treatment, but also of lowering dosage and cost,and eliminating wasted medicine.

This new insight comes via the tapeworm Hymenolepis diminuta, a speciesfound in rats and long used as a research model by parasitologists. By sortingthrough the soup of biochemicals the tapeworm uses to influence muscle activityin the gut, a group led by John Oaks of the School of Veterinary Medicine,and Paul Bass of the School of Pharmacy, has isolated a chemical signalfactor that may help prolong the time it takes for medicines to move throughthe small intestine.

"Most oral medications would benefit from prolonged small intestinalresidence," says Bass, an emeritus professor of pharmacy. "Almostall drugs we take orally are absorbed from the small intestine. By prolongingthe medication's residence time in that organ, we should enhance its absorptionand obtain higher blood levels of the medication."

The compound characterized by Oaks and Bass, known in scientific shorthandas cyclic GMP, is a member of a family of compounds known generically assignal factors. Its role is to alter the electrochemical activity of themuscles in the intestine, slowing or shutting down intestinal transit ofthe host, actions that help the tapeworm obtain a meal or otherwise survivein an organ designed to quickly sweep food along.

"Inside cells, cyclic GMP is a signal molecule," notes Oaks,a professor of comparative bioscience. "It tells cells how to behave.When the tapeworm secretes this signal molecule, the intestine closes offand nothing moves. That suggested to us that the intestine is not digestingmaterial as it normally would."

The cyclic GMP compound, Oaks adds, is cheap and easy to synthesize.Its use as an additive to medicines has been patented by the Wisconsin AlumniResearch Foundation.

"Many drugs are absorbed at less than 50 percent from the intestine,"says Oaks. "The key will be can we use cyclic GMP with certain kindsof drugs to increase their level of uptake into the blood?"

Other potential benefits associated with lower dosages include lessenedside effects and fewer chemicals released into the environment. A recentsurvey of surface water in the United States revealed a growing presenceof drugs in the environment. The suspected sources are medicines that arenot completely metabolized by the humans and animals they are administeredto.

"If we could halve the dosage, we could lower the percentage ofnonabsorbed drug that ends up in the environment," says Oaks.

The work done by the Wisconsin team, which also included K. Dubear Kroeningand Noah P. Zimmerman, was funded in part by a grant from the National Institutesof Health.