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Prospects for new malaria interventions



Credit: The Royal Society

April 25 is World Malaria Day, an international event that is celebrated each year in recognition of the global effort to fight malaria, one of the oldest and deadliest diseases in the world. This year's motto "Ready to be Malaria" underlines the common goal and commitment of the global malaria family. In a recent review in Open Biology David Baker, a professor of malaria parasite biology at the London School of Hygiene and Tropical Medicine, discusses the problem of drug resistance in the fight against malaria and a promising molecular pathway that can help This.

Although the number of clinical cases of malaria and resulting deaths has decreased significantly in the last 20 years, more than 400,000 people die of malaria every year; Most of them are children in Africa. One of the biggest challenges in the fight against malaria is the development and spread of drug-resistant malaria parasites. When resistance to any new antimalarial drug occurs, it becomes necessary to combine two or more component drugs to slow the spread of resistance. The main drug currently recommended for malaria treatment is based on combinations containing an artemisinin derivative. Artemisinin is a medicine from a plant that works very fast against malaria. Chinese scientist Tu Youyou received a Nobel Prize in 201

5 for her work on the discovery of this drug in the 1970s. Almost inevitably, treatment errors in artemisinin combinations become more common, especially in parts of Southeast Asia.

It is therefore urgent to develop new antimalarial drugs to prevent the recurrence of malaria that would occur in the event of failed treatments with artemisinin. There are several promising new malaria drugs in clinical trials, but the Malaria Venture Medicines (MMV) have estimated that only 8% of candidates undergoing formal preclinical testing are actually admitted to the clinic. In view of this high rate of erosion, it is important that alternative targets and biochemical pathways in the malaria parasite (Plasmodium species) be explored to develop future generations of antimalarial drugs that must continue and expand the success of malaria elimination programs in affected countries

Credit: The Royal Society

Why Cyclic Nucleotide Signaling in Malaria Parasites?

One such biochemical path explored by David Baker's team at the London School of Hygiene and Tropical Medicine (LSHTM) is called the cyclic nucleotide signaling pathway. These are actually two closely related pathways in which the intracellular messenger molecules cyclic AMP (cAMP) and cyclic GMP (cGMP) are the key players. These molecules are present in virtually all life forms including humans and malaria parasites and have very different functions in all animal species. These molecules are not themselves the prospective drug targets, but the enzymes that synthesize, or degrade, or become activated by them are the targets, as these enzymes are significantly different in humans and malaria parasites. Therefore, a drug that is designed to block the activity of the parasitic version of the enzyme does not affect the human enzyme, which makes the drug safe.

Professor Baker's group and other researchers around the world have shown that many enzymes of this pathway are essential for the development of multiple stages of the complex life cycle of malaria parasites, so drug targeting should be effective. Another positive aspect of this pathway as a potential target for drugs is that key components such as protein kinases and phosphodiesterases are known to be good targets for other human diseases and disorders with numerous effective drugs already used in the clinic for the treatment of various cancers erectile dysfunction.


Further information:
Experts are identifying ways to combat drug-resistant parasites that cause malaria

Further information:
David A. Baker et al. Cyclic Nucleotide Signaling in Malaria Parasites, Open Biology (2017). DOI: 10.1098 / rsob.170213

Citation in Journal:
Open biology

Provided by:
The royal society


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