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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.

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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Protein Consumption May Reduce The Risk of Atrial Fibrilliation (Heart Rhythm Disorder) in Women: Research

Women with the lowest protein intake -- which was roughly equivalent to the current recommended daily amount of protein in the US

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Heart Rate
The research is scheduled to be presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology on March 28-30 in the US. Pixabay

 Women who ate slightly more than the recommended daily amount of protein were significantly less likely to develop atrial fibrillation (AFib), a dangerous heart rhythm disorder that can lead to stroke and heart failure, say researchers.

“Women with the lowest protein intake — which was roughly equivalent to the current recommended daily amount of protein in the US — had the highest incidence of AFib, and eating a little more was protective, even after taking into account other factors that can predispose someone to develop AFib,” said the study’s lead author Daniel Gerber from Stanford University in the US.

“This modifiable risk factor for AFib may be a fairly easy way for women to potentially lower their risk,” Gerber added. According to the researchers, protein is an important part of women’s diets, especially as they age, because it can help prevent frailty and loss of bone mass and lean muscle mass.

Current US guidelines recommend consuming 0.8 grams of protein per kilogram of bodyweight, which for a 140-pound person is about 51 grams per day. The analysis of over 99,000 postmenopausal women (median age of 64 years) from the Women’s Health Initiative Randomised Controlled Trials and Observational Study found that those who ate 58-74 grams of protein a day were 5-8 per cent less likely to develop AFib, but there seemed to be a ceiling effect after eating more than 74 grams, at which point the benefit was no longer statistically significant.

Of the nearly 100,000 women in the study, 21,258 (21.3 per cent) developed new AFib during the average 10-year follow up period. Researchers excluded women with existing heart rhythm issues and had a two-year run-in period to be sure women didn’t have any signs of occasional AFib.

They assessed protein intake using a food questionnaire, and these reports were adjusted using validated urine tests to confirm how much protein was consumed. The women were then grouped into four quartiles based on protein intake (below 58 g/day, 58-66 g/day, 66-74 g/day and below 74 g/day) and then assessed for new cases of AFib.

Egg Sandwich, Egg, Bread, Yolk, Boiled Eggs
Women who ate slightly more than the recommended daily amount of protein were significantly less likely to develop atrial fibrillation (AFib), a dangerous heart rhythm disorder that can lead to stroke and heart failure, say researchers. Pixabay

The average protein intake was 60 grams/day, with women who ate between 58 and 74 grams a day having significantly less risk of AFib. This relationship remained even after adjusting for age, ethnicity, education and other cardiovascular conditions and risk factors such as body mass index, physical activity, tobacco and alcohol use, high blood pressure, high cholesterol, diabetes, coronary and peripheral artery disease and heart failure.

Interestingly, women typically underestimated their daily protein intake by about 10 grams and caloric intake by 600-700 calories, which speaks of the need for more nutritional awareness and education, researchers said. “Based on our findings, it seems that eating more protein may not only help strengthen women physically, but it may also have cardiovascular benefits in terms of reducing AFib and related death, strokes and heart failure,” Gerber said.

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The research is scheduled to be presented at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology on March 28-30 in the US. (IANS)