Scientists searching for new drugs to fight malaria have identified a number of compounds -- some of which are currently in clinical trials to treat cancer -- that could add to the anti-malarial arsenal.
Duke University assistant professor Emily Derbyshire and colleagues identified more than 30 enzyme-blocking molecules, called protein kinase inhibitors, that curb malaria before symptoms start.
By focusing on treatments that act early, before a person is infected and feels sick, the researchers hope to give malaria –- especially drug-resistant strains –- less time to spread.
The findings appear online and are scheduled to appear in a forthcoming issue of the journal ChemBioChem.
Malaria is caused by a single-celled parasite called Plasmodium that spreads from person to person through mosquito bites. When an infected mosquito bites, parasites in the mosquito's saliva first make their way to the victim's liver, where they silently grow and multiply into thousands of new parasites before invading red blood cells -- the stage of the disease that triggers malaria's characteristic fevers, headaches, chills and sweats.
Most efforts to find safe, effective, low-cost drugs for malaria have focused on the later stage of the infection when symptoms are the worst. But Derbyshire and her team are testing chemical compounds in the lab to see if they can identify ones that inhibit malaria during the short window when the parasite is still restricted to the liver, before symptoms start.
One of the advantages of her team's approach is that focusing on the liver stage of the malaria lifecycle -- before it has a chance to multiply -- means there are fewer parasites to kill.
Using a strain of malaria that primarily infects rodents, Derbyshire and Jon Clardy of Harvard Medical School tested 1,358 compounds for their ability to keep parasites in the liver in check, both in test tubes and in mice.
"It used to be that researchers were lucky if they could identify one or two promising compounds at a time; now with advances in high-throughput screening technology we can explore thousands at once and identify many more," said Derbyshire, an assistant professor in the Departments of Chemistry and Molecular Genetics and Microbiology at Duke.
Focusing on a particular group of enzyme-blocking compounds called protein kinase inhibitors, they identified 31 compounds that inhibit malaria growth without harming the host. Several of the compounds are currently in clinical trials to treat cancers like leukemia and myeloma.
The same compounds that stopped the stage of malaria that lurks in the liver also worked against the stage that lives in the blood.
Malaria-free mice that received a single dose before being bitten by infected mosquitos were able to avoid developing the disease altogether.
Medicines for malaria have been around for hundreds of years, yet the disease still afflicts more than 200 million people and claims hundreds of thousands of lives each year, particularly in Asia and Africa. Part of the reason is malaria's ability to evade attack. One of the most deadly forms of the parasite, Plasmodium falciparum, has already started to outsmart the world's most effective antimalarial drug, artemisinin, in much of southeast Asia. Infections that used to clear up in a single day of treatment now take several days.
Diversifying the antimalarial arsenal could also extend the lifespan of existing drugs, since relying less heavily on our most commonly used weapons gives the parasite fewer opportunities to develop resistance, Derbyshire said.
Another advantage is that the compounds they tested suppress multiple malaria proteins at once, which makes it harder for the parasites to develop ways around them.
"That makes them like a magic bullet," she said.
The research was supported by Duke University, Harvard Medical School and the National Institutes of Health (Grant Number: GM099796)
CITATION: "Chemical interrogation of the malaria kinome," Derbyshire, E. and Clardy, J., et al. ChemBioChem, 2014. http://dx.doi.org/10.1002/cbic.201400025
Robin Ann Smith | Eurek Alert!
Penn researchers use network science to help pinpoint source of seizures
29.01.2016 | University of Pennsylvania
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.
Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...
NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.
Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...
In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.
In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...
The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).
“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...
02.02.2016 | Event News
26.01.2016 | Event News
26.01.2016 | Event News
05.02.2016 | Life Sciences
05.02.2016 | Materials Sciences
05.02.2016 | Physics and Astronomy