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Scientists hope to end sleeping sickness by making parasite that causes it self-destruct
Date:1/15/2010

tendency to bite its victims around the lips, in South and Central America. The parasite that causes Chagas is the world's leading cause of heart disease, and the life expectancy for patients with chronic symptoms decreases by an average of nine years.

Leishmaniasis, a disease transferred by the biting female sandfly, is prevalent in four continents and comes in four varieties, all of which either disfigure or kill its hosts. One causes skin ulcers; another causes chronic lesions resembling leprosy; the third destroys the mucus membranes in the nose, mouth and throat; the fourth causes high fever, organ swelling and, if left untreated, has a fatality rate as high as 100 percent within two years.

Screening for trypanosomal diseases is challenging, because they most often affect people in remote locations with few or no medical resources, and existing treatments lack specificity and can cause severe side effects.

Lepesheva and her team sought to damage the single-celled parasite's cellular membrane, knowing that if they could weaken that barrier, the regulation of the intercellular environment would be disrupted, and the parasite would die.

"It has been known for some time that T. brucei, the parasite that causes sleeping sickness, consumes cholesterol in its human host's blood to shore up the cellular membrane, and researchers presumed there was no getting around that," Lepesheva said. "But we suspected the parasite, like plants and animals, still might need to make its own sterols for growth and development -- functional sterols that could be targeted and inhibited."

The team chose to attack the parasite's enzyme known as 14DM, which is short for sterol 14α-demethylase. They picked 14DM because it has a counterpart in fungi, which cause athlete's foot and ringworm, and such fungal infections are commonly treated with drugs that prevent 14DM from making ergosterol, a sterol required for membrane synthesis.


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Contact: Angela Hopp
ahopp@asbmb.org
301-634-7389
American Society for Biochemistry and Molecular Biology
Source:Eurekalert  

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