March 30, 2010
Contact:
Jeremy Craig, 404-413-1357
University Relations
ATLANTA - Chemists W. David Wilson and David W. Boykin are using a recent $1.8 million grant from the National Institutes of Health to continue their work in the search for more effective drugs to treat a deadly parasitic disease.
Wilson and Boykin, Regents' Professors of chemistry, are on the trail of better understanding the mechanisms of the organism, Trypanosoma brucei, called a trypanosome, which causes African sleeping sickness - a fatal disease borne by the tsetse fly - which should in turn lead to better compounds for targeting the disease.
The microorganism is sheathed in a complex surface containing sugary proteins called glycoproteins. The antibodies of the human immune system can recognize the disease by its proteins, but the trypanosome can change the proteins on the surface, causing the immune system to need to create a new antibody to attack the trypanosome.
"You'll die before you can make a thousand different antibodies," Wilson said. "In the meantime, the tsetse flies continue to bite, filling them with the trypanosome and further spreading the disease."
Wilson and Boykin are working on drug compounds that target the genetic code of the trypanosome, altering the structure of the DNA and killing the organism.
The current treatments for African sleeping sickness have not changed in structure since the early 20th century, and some contain toxic arsenic.
"The goal is to deliver safer drugs in smaller doses that are more selective in targeting the kinetoplast of the trypanosome,"Wilson said.
One way to reduce the toxicity might be to use a very specific molecule that could cause the needed distortions to tear apart the kinetoplast, he said.
"This means that you could use a much smaller dose to have an effect on the trypanosome," Wilson said, "and immediately, toxicity problems will become less, thus making it a more effective compound."
A few years ago, the latest compound developed from the Wilson and Boykin laboratories, pafuramidine, was used in trials to help treat people living in the Republic of the Congo who had African sleeping sickness. However, the drug failed during the phase III trials - the last phase of drug testing - as mandated by the U.S. Food and Drug Administration due to toxicity levels.
"It's probably possible to reformulate the compound and get it approved, but we think that we've already got better compounds," Wilson said. "We're moving into the second generation of compounds."
Fundamentals learned from the research may also have other applications in other diseases, Wilson said.
Wilson and Boykin's research is also supported by the Bill and Melinda Gates Foundation.