Researchers unlock how key drug kills tropical parasites

November 10, 2010
Charles Mackenzie, a professor of veterinary pathology, works with elephantiasis patients in Tanzania. Credit: Courtesy photo

In a major breakthrough that comes after decades of research and nearly half a billion treatments in humans, scientists have finally unlocked how a key anti-parasitic drug kills the worms brought on by the filarial diseases river blindness and elephantitis.

Understanding how the drug ivermectin works has the potential to lead to new treatments for the diseases, in which the body is infected with parasitic , said Charles Mackenzie, a professor of veterinary pathology in the College of Veterinary Medicine and researcher on the project. The diseases afflict about 140 million people worldwide, doing much of their damage in equatorial Africa.

"Ivermectin is one of the most important veterinary and human anti-parasitic agents ever," Mackenzie said. "Knowing specifically how it interacts with the body's own immune system and kills parasitic worms opens up whole new treatment avenues."

The research appears in the current edition of the .

Elephantiasis () is caused by tiny worms spread via mosquitoes and results in severe swelling of the legs, arms and torso. River blindness (onchocerciasis) is spread by black flies, and after the worms die in a person's eye, they can cause blindness and debilitating .

Ivermectin works by killing the first stage of the worm in the human body, and also appears to paralyze the reproductive tract of the adult female worms, stopping reproduction of new parasites.

What the researchers discovered is that the drug does this by preventing the worm from secreting proteins through a pore in its mid-body; ivermectin binds to receptors at the pore and blocks the secretions. It is the secretions that normally block a person's ability to attack and kill the worm; after the drug prevents them, the host's own immune system is able to attack and kill the parasites.

"Understanding how the worms were avoiding the host's immune responses will greatly enhance our ability to manipulate the to the advantage of the host, and perhaps develop vaccines," Mackenzie said. "Also, one of the most important challenges in the overall effort against filarial infections relates to the development of resistance and the loss of efficacy of the drugs we use; this new knowledge provides an important key to understanding and perhaps preventing resistance."

Ivermectin was developed by pharmaceutical firm Merck & Co. in the 1970s from a soil fungus. It was donated in 1987 for use to treat , as existing drugs were in fact inducing blindness. Ivermectin was able to be used safely in mass drug administration programs in many developing countries, shifting the paradigm for how public health programs delivered medicines in rural areas. The drug then was used in other parasitic disease programs, such as the one for elephantiasis, treating more than 100 million people for that disease.

Mackenzie has worked for more than 20 years on tropical filarial diseases, much of that time partnering with Tim Geary at McGill University in Montreal. Geary's lab was critical in the ivermectin findings, as was McGill graduate student Yovany Moreno. Geary and Mackenzie also recently were awarded $2 million from the Gates Foundation to study another anti-filarial drug, flubendazole.

Explore further: New drug resistance found in river blindness

Related Stories

New drug resistance found in river blindness

June 15, 2007

A 20-year effort to control the spread of onchocerciasis, or river blindness, in African communities is threatened by the development of drug resistance in the parasite that causes the disease, a study by McGill University ...

The onchocerciasis parasite showing signs of resistance

January 31, 2008

Onchocerciasis is an infection caused by Onchocerca volvulus, a parasite nematode worm transmitted to humans by a species of black fly of the Simulium genus whose larvae develop in fast-flowing rivers. Infected subjects suffer ...

Recommended for you

Yarn from slaughterhouse waste

July 29, 2015

ETH researchers have developed a yarn from ordinary gelatine that has good qualities similar to those of merino wool fibers. Now they are working on making the yarn even more water resistant.

Findings illuminate animal evolution in protein function

July 27, 2015

Virginia Commonwealth University and University of Richmond researchers recently teamed up to explore the inner workings of cells and shed light on the 400–600 million years of evolution between humans and early animals ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.