Worm cell death pathway to drugs for deadly parasite

Last Updated: Saturday, October 8, 2011 - 13:27

Washington: Researchers have for the first time identified a "programmed cell death" pathway in parasitic worms which they claim could one day lead to treatments for schistosomiasis, one of the world`s most serious diseases.

A team at the Walter and Eliza Hall Institute, led by Dr Erinna Lee and Dr Doug Fairlie, programmed cell death (also called apoptosis) in human cells. They have recently started studying the process in schistosomes, parasitic fluke worms responsible for the deadly disease.

Dr Lee said that the group has shown that, unexpectedly, the cell death machinery that exists in fluke worms is remarkably similar to cell death pathway in human cells, the
`Proceedings of the National Academy of Sciences` reported.

"We found that schistosomes have a complex cell death mechanism that relied on a delicate balancing act of pro-survival and pro-death molecules, just like in humans," Dr Lee said.

"Using the Australian Synchrotron, we also determined that the three-dimensional structure of a key schistosome cell death molecule was very similar to the protein which controls the process in humans. This structure is important because it will potentially guide future efforts to design drugs that target the schistosome cell death pathway," she added.

More than 700 million people worldwide are at risk of schistosomiasis and 200 million people are currently infected, 85 percent of whom live in Africa. Each year, an estimated
200,000 people die from the disease.
The parasitic worm is carried by freshwater snails in contaminated water systems, and causes damage to the spleen, liver and other organs that can be fatal.

Dr Fairlie said that there is only one drug widely used for treating schistosomiasis, and concerns about the potential for drug resistance have increased the urgency for new drug targets and treatments.

The researchers said the team are currently exploring the possibility that so-called "BH3 mimetic" compounds such as ABT-737, discovered by biotechnology company Abbott, could also have a niche application for the treatment of parasitic worm diseases such as schistosomiasis.

BH3 mimetics target the cell death pathway in humans and are currently being trialled as anti-cancer agents.

Dr Lee said: "The Bcl-2-regulated cell death pathway is currently being investigated as a therapeutic target for the treatment of some cancers.

"We have found that a BH3-mimetic compound called ABT-737 binds to at least one schistosome pro-survival protein suggesting it is feasible that BH3-like molecules could also be developed for treating schistosomiasis, and potentially other parasitic worm infections."

PTI



First Published: Saturday, October 8, 2011 - 13:27

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