2 hours ago by Deirdre Branley Credit: CDC

Each year nearly 600,000 peoplemostly children under age five and pregnant women in sub-Saharan Africadie from malaria, caused by single-celled parasites that grow inside red blood cells. The most deadly malarial speciesPlasmodium falciparumhas proven notoriously resistant to treatment efforts. But thanks to a novel approach developed by scientists at Albert Einstein College of Medicine of Yeshiva University and described in the January 20 online edition of ACS Chemical Biology, researchers can readily screen thousands of drugs to find those potentially able to kill P. falciparum.

Scientists have known for more than a decade that malaria parasites have an Achilles heel: Like all cells, they require two key building blockspurines and pyrimidinesto synthesize their DNA and RNA. But malaria parasites can't synthesize purines on their own. Instead, they must import purines from the host red blood cells that they invade. A parasite protein called PfENT1 transports purines from blood cell into the parasites. So drugs that block PfENT1 could conceivably kill the parasites by depriving them of purines they needbut an experimental approach for identifying PfENT1 inhibitors didn't exist, until now.

Einstein's Myles Akabas, M.D., Ph.D., developed a novel yeast-based high-throughput assay for identifying inhibitors of the PfENT1 transporter. Dr. Akabas worked with two MSTP students in his lab (I.J. Frame and Roman Deniskin) as well as colleagues at Einstein (Drs. Ian Willis and Robyn Moir) and Columbia University (Drs. Donald Landry and David Fidock). The researchers used their technique to screen 64,560 different compounds. They identified 171 potential antimalarial drugs. Studies of nine of the most potent drugs showed that they kill P. falciparum parasites in laboratory culture.

"We've shown that the PfENT1 transporter is a potential drug target for developing novel antimalarial drugs," said Dr. Akabas, senior author of the ACS Chemical Biology paper and a professor of physiology & biophysics, of medicine and in the Dominick P. Purpura Department of Neuroscience at Einstein. "By using our rather simple approach, scientists could create similar high-throughput screens to identify inhibitors for killing other parasites that rely on transporters to import essential nutrients."

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Scientists develop novel technique for finding drugs to combat malaria

Researchers at the Massachusetts Institute of Technology (MIT) have developed a new method for tackling diabetes that could represent a significant breakthrough in treating the condition. The team's engineered insulin stays in the patients bloodstream, but is only activated when sugar levels start to tip the scales.

There have been some promising developments in diabetes research over recent months. Back in October, stem cell researchers at Harvard University revealed a breakthrough on the road towards a cure for the condition via a means of creating human insulin-producing beta cells. More recently, a University of Alabama at Birmingham study showed that high blood pressure drugs have the ability to reverse the disease in animal models.

The new MIT study isnt centered on a cure for the condition, but focuses instead on developing a better method of treatment for patients.

Type 1 diabetes patients use insulin injections to make up for a lack of the hormone in their bloodstream. Some make use of a long-acting treatment that stays in the system for 24 hours, while others keep tabs on their calorie intake and blood sugar levels to determine how much to inject. Both of these methods act independently of the patients blood sugar levels.

Researchers at MIT have developed a new form of treatment that not only circulates for a long period of time, but is only activated when blood sugar levels get too high. This would provide a more efficient method of dealing with glucose spikes over extended periods of time.

To create the new, glucose-responsive treatment, the researchers made two modifications. Firstly, in order to ensure that the engineered hormone stays in the bloodstream for the required length of time, a hydrophobic molecule known as an aliphatic domain was added. Its not known for certain why the chain of fatty molecules prolong the molecules lifespan in the bloodstream, though its thought that it may bind to proteins, preventing the insulin from tackling sugar molecules.

Secondly, researchers added PBA a chemical group that reversibly binds to glucose, thus bringing it into contact with the insulin when high levels of sugar present themselves. The team created four different variants of the engineered molecule, each containing PBA with a different chemical modification, such as fluorine or nitrogen.

To test the effectiveness of the treatment, experiments were carried out on insulin-deficient mice, measuring the response of their blood sugar levels to surges in glucose over 10 hours. The results showed that the engineered insulin containing PBA with fluorine responded fastest to the spikes, winning out against the other chemically-modified treatments, as well as traditional regular and long-acting insulin.

While further testing is required before the engineered insulin could be used in routine treatment, it could mark a significant advance in how the condition is tackled, providing a more efficient alternative to existing treatments. The MIT team plans to continue its research, working to improve the performance of the modified insulin, making it safer and more efficient.

Source: MIT

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MIT researchers develop glucose-responsive diabetes treatment