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One drug is 'new hope' for three killer infections

One drug is 'new hope' for three killer infections
09.08.2016 16:30
One drug can treat three deadly and neglected infections - Chagas disease, leishmaniasis and sleeping sickness - animal studies show.

It has been described as a "new hope" for tackling the parasitic infections which affect millions of people in the poorest parts of the world.

The discovery, reported in the journal Nature, was made by testing three million compounds.

The new drug is now entering safety tests before human trials.

The three diseases are all caused by similar parasites, leading scientists to believe one therapy might be useful against the trio.
Sleeping sickness is caused by the Trypanosoma brucei parasite, which is spread by the bite of the tsetse fly. The disease is officially known as Human African trypanosomiasis, but takes its more common name from the coma that results when the parasite penetrates the brain. It is found in sub-Saharan Africa.

Chagas disease - or America trypanosomiasis - is caused by the Trypansosoma cruzi parasite. It can cause the heart and digestive system to become enlarged, which can be deadly. The "kissing" or "assassin" bug spreads the parasite. Chagas mostly affects people in Latin America, but has now spread to other continents.

Leishmaniasis is caused by infection with Leishmania parasites and is spread by the bite of sandflies. It causes a wide range of symptoms depending on which part of the body is infected, ranging from anaemia and fever to the total destruction of the lining of the nose, mouth and throat. It is found in the Americas, Africa and Asia.

Combined, the three parasites infect 20 million people and kill 50,000 each year, the research team said.

While there are some drugs to treat the infections, they are expensive and toxic and often need to be given via an intravenous drip, making them impractical in poor regions.

The researchers tested three million compounds, made by the pharmaceutical company Novartis, to find those that could kill multiple parasites in the laboratory.

One was then used as the basis of thousands of modifications to make the original 20 times more potent.

Tests then showed the upgrade - codenamed GNF6702 - could treat Trypanosoma brucei, Trypansosoma cruzi and Leishmania infections in mice.

Dr Elmarie Myburgh, one of the researchers based at the University of York, told the BBC News website: "What makes it special is the fact it is targeting all three parasites. That's the first time it has been done, so it is quite special.

"To me this is obviously a big deal, I'm in this field to try and make a difference, to get to a cure, and we're working hard in the hope that it gets to patients.

"There's been very little incentive to spend a lot of money on these diseases as they affect a very poor, and yet large, population."

Further refinements to the compound are taking place as the researchers ensure it is safe before starting human trials.

Recycling centres

The drug works by attacking the parasites' proteasomes. The structures recycle waste proteins in the parasite.

But crucially the chemical does not affect similar processes in mammalian cells.

Richard Glynne, from the Genomics Institute of the Novartis Research Foundation, told the BBC that attacking the proteasome was "not by design, more by serendipity".

It had been thought the proteasome was too similar across all species to develop a drug that would not be toxic to the patient.
However, he said there may ultimately need to be three separate drugs: "It may be a single drug for all three diseases may not be the best strategy.

"The biology of the diseases is different. For example in sleeping sickness the parasite is in the brain, so you need a drug that gets into the brain, so there are tweaks that may be required."

Dr Stephen Caddick, the director of innovation at the Wellcome Trust research charity which helped fund the study, told the BBC News website: "These are pretty nasty, highly prevalent parasites and affect people living in the most poverty-stricken parts of world. We need to make more progress.

"We continually face challenges getting medicines to those people and making affordable medicines is an important first step.
"This is quite an important piece of research, I'm excited by it, but there's still a long way to go."

(BBC)

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