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Scientists at Massachusetts Institute of Technology and Harvard University Discover Malaria Achilles Heel

The experiments include seeing how well each of the 12 compounds works, for how long, and whether resistance develops with any of the promising agents

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Infected mosquito. Image Source: Wikimedia Commons.
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September 10, 2016: Scientists appear to have discovered malaria Achilles heel, a weakness common to the multiple stages of malaria infection. In doing so, they have found a compound that cured mice of the disease.

Once it’s entered the body through the bite of an infected mosquito, the malaria parasite, P. falciparum, behaves as a unique organism as it goes through three phases during its life cycle. Experts say most treatments are aimed at only one stage or another. Over time, the parasite can become resistant to therapy, sometimes as quickly as within one year.

But researchers at the Broad Institute of Massachusetts Institute of Technology and Harvard University have identified a single protein target that appears to be the disease’s weakness, according to senior researcher Stuart Schreiber, a founding member of the biomedical institution.

Malaria Infection. Image Source: Wikimedia Commons.
Malaria Infection.
Image Source: Wikimedia Commons.

Malaria protein

“We did discover a novel protein that’s made by the parasite, that’s needed for all three phases of its life cycle, and a series of novel compounds that potently inhibit this protein,” he said. “And we could show in an infected animal that we could kill the parasite in all three phases.”

Schreiber and colleagues published their findings in the journal Nature.

After discovering the protein, researchers screened a unique library of 100,000 small molecules, from which they synthesized about a dozen compounds that they tested in infected mice. The molecules appear to stop the production of this protein in all of malaria’s life stages, effectively killing the disease.

The mice were disease-free for a month, a length of time considered to be a cure. When they tried to infect other mice with the blood of the treated rodents, the animals did not become infected with malaria.

The compound that scientists tested was a one-time oral treatment. Schreiber was quick to caution that what works in a mouse is not necessarily effective in humans. But he is hopeful.

“I am the eternal optimist,” he said. “On the other hand, I do know that what’s ahead is extremely challenging and full of unknowns that can only be addressed by marching forward and running the key experiments.”

The experiments include seeing how well each of the 12 compounds works, for how long, and whether resistance develops with any of the promising agents.

In theory, Schreiber said a drug that works in all three stages of malaria could be taken at any point in the disease cycle, as a treatment and even as a way to prevent the disease.

The researchers note that individuals can remain infectious even while undergoing treatment. So their infection can be spread to someone else through a mosquito bite.

Information about the anti-malaria compounds is being made freely available to other researchers through an online database. The library contains compounds designed and housed at the Broad Institute that are not usually found in the arsenals of pharmaceutical companies.

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Malaria infects over 200 million people each year. Once it has infected a human host, the malaria parasite evolves through a number of unique stages, from initial blood infection to liver infiltration where the parasite matures and reenters the blood stream.

The parasite then goes on to infect and destroy red blood cells, releasing thousands of daughter parasites that invade other blood cells, continuing the cycle of reproduction and infection.

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It is during this later blood stage when symptoms of malaria occur, including very high fever, overwhelming sweating, debilitating nausea and diarrhea. Over half a million people do not survive, mostly children in sub-Saharan Africa.

The research by Schreiber and colleagues was funded by the Bill and Melinda Gates Foundation. A Japanese drug company, Eisai, has shown an interest in helping to further develop the experimental malaria treatment. (IANS)

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Kidney disease may increase the risk of Diabetes: says a study

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Kidney disease may increase the risk of diabetes.
Kidney disease may increase the risk of diabetes. IANS

New York, Dec 12: If you are suffering from kidney dysfunction, you may be at high risk of developing diabetes, finds a study.

The risk may be attributed to the rising level of urea — the nitrogen-containing waste product in blood, which comes from the breakdown of protein in foods.

Kidneys normally remove urea from the blood, but it can build up when kidney function slows down, resulting in greater insulin resistance as well as secretion in the body.

“We have known for a long time that diabetes is a major risk factor for kidney disease, but now we have a better understanding that kidney disease, through elevated levels of urea, also raises the risk of diabetes,” said the Ziyad Al-Aly, Assistant Professor at the Washington University in St. Louis.

“When urea builds up in the blood because of kidney dysfunction, it often results in increased insulin resistance and impaired insulin secretion,” Ziyad added.

The findings, published in the journal Kidney International, are significant because urea levels can be lowered through medication, diet — for example, by eating less protein — and other means, thereby allowing for improved treatment and possible prevention of diabetes, the researchers said.

For the study, the team evaluated the records of 1.3 million adults without diabetes over a five-year period, beginning in 2003.

Out of these, 117,000 of those without diabetes — or 9 per cent — had elevated urea levels, signalling poor kidney function and were at 23 per cent higher risk of developing diabetes. (IANS)