Early step in sleeping sickness cure

By Julie Gould
Science reporter, BBC News

Image caption,
The parasite trypanasoma gambiense is the leading cause of sleeping sickness

Scientists have taken a tentative step towards creating a cure for the most common form of sleeping sickness.

The gambiense strain of the trypanosoma parasite is resistant to proteins the immune system produces to fight the infection.

Belgian researchers have developed a mutant version of the protein, which early tests show can kill a wide range of trypanosomes including gambiense.

The gambiense strain causes more than 97% of sleeping sickness cases in western and central Africa. According to the World Health Organization, there were 7,197 cases in 2012.

Parasite defences

The immune system produces apoL1 to try to attack the parasite.

In the study, researchers from the Universite Libre de Bruxelles outlined how gambiense evolved a three-part defence mechanism against the protein apoL1.

ApoL1 is normally taken up by the trypanosoma parasites, as it tricks the parasite into believing that it is beneficial.

The protein then embeds itself into the walls of the gut membrane, where it kills the parasite.

Image caption,
The parasite is spread by the tsetse fly

The first step in gambiense defence is they "create a protein that stiffens the membranes against the apoL1 protein," said Prof Etienne Pays, lead author of the research. "This acts as a barrier."

The second stage is to make it more difficult for the parasite to absorb the protein.

Finally, if the protein was to get through the other barriers, gambiense is able to digest apoL1 quicker than other forms of the parasite, so that it cannot be absorbed by membranes.

Prof Pays said: "The crucial thing here is that apoL1 is still there. It has not been absorbed. It can still be used to kill the parasite."

This led Prof Pays and his team to develop a mutant strain of apoL1. This not only kills gambiense, but "it kills all African trypanosomes, pathogenic for humans or for cattle".

But Prof Pays said the research was still in the early stages.

"Needless to say, this is a promising discovery," he added.

"However, it remains to be seen if this apoL1 variant could be used to treat sleeping sickness. In the blood, this protein could be either unstable or toxic in itself, so more work is needed to appreciate the potential of this finding."

In 1998, the same group of researchers discovered how rhodesiense, another strain of the parasite trypanosome, resisted our defences.

Rhodesiense uses an anti-protein to disable apoL1 so that we cannot fight against it.

Wendy Gibson, professor of protozoology at the University of Bristol, who has been studying the evolution of trypanosome said: "They've finally solved the mystery of how the gambiense has been fighting our defences. It is a meticulous piece of work."

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