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Medical News Today: Promising drug candidate tackles malaria in a new way

A new study reports a breakthrough with a new experimental antimalaria drug that appears to overcome the problem of drug resistance in the disease-carrying Plasmodium parasite.
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The new compound offers potentially long-lasting effects in preventing and treating malaria.

Malaria is a life-threatening disease that kills around 600,000 people worldwide every year - most of them sub-Saharan children under the age of 5. The disease is caused by various species of the Plasmodium parasite, which infects humans via mosquito bites.

Once in the body, Plasmodium reproduces in the liver and infects red blood cells. If untreated, malaria disrupts blood supply to organs, which eventually leads to death.

While antimalaria treatments exist, there is growing evidence that the malaria parasite is becoming increasingly resistant to them. Earlier this year, researchers warned that the advance of resistant strains of Plasmodium poses a serious global threat.

Many researchers say what is needed in the ongoing battle against malaria is new drug combinations that are easy to use and are broadly effective against all stages of the disease.

In the journal Science Translational Medicine, a group that includes members from the Eskitis Institute for Drug Discovery at Griffith University in Australia describes how a new compound - known as DSM265 - offers potentially long-lasting effects in preventing and treating malaria.

The study shows how DSM265 also kills Plasmodium falciparum in the blood and liver. P. falciparum is the deadliest of the human malaria parasites and the one that kills the most people. It is also one of the two strains - Plasmodium vivax being the other - that is becoming increasingly resistant to current drugs.

The researchers, who ran tests on parasite isolates and also in mice and dogs, say DSM265 has the potential to be used - in combination with other drugs - either as a single-dose treatment for people infected with malaria or as a once-weekly dose for ongoing prevention of the disease.

Drug targets essential enzyme DHODH

DSM265 works by attacking Plasmodium's ability to make building blocks for generating its own genetic material - DNA and RNA. These building blocks are nucleotides - DNA and RNA are long chains of various kinds of nucleotides.

One of the raw materials that the parasite needs to make the nucleotides is pyrimidine. To make pyrimidine, it needs an enzyme called dihydroorotate dehydrogenase (DHODH). DSM265 deactivates this enzyme.

The researchers say DSM265 offers two important advantages over current treatments - it does not have to be taken every day and it also attacks the parasite in its liver stage.

The study follows news last month of another novel antimalarial compound, DDD107498, details of which are published in Nature.

DDD107498 has the potential to address a range of clinical needs - including single-dose treatment, prevention of spread to others and protection against becoming infected in the first place.

That discovery came as a result of a collaboration between the Drug Discovery Unit at the University of Dundee in the UK and Medicines for Malaria Venture - a not-for-profit public-private partnership that includes some of the Eskitis research team.

'Quite amazing' to have two new drugs, two new targets

Co-author Professor Vicky Avery, who heads a research group at the Eskitis Institute, says it "is quite amazing" to be moving forward with two new candidate compounds, each with a new drug target - an achievement she puts down to the strong collaboration between the teams. She notes:

"Having compounds which are working through new mechanisms is critical for overcoming the ever growing concerns with drug resistance."

The next steps, Prof. Avery adds, will focus on how safe and effective the drugs are in humans and to find out whether they fulfill the promise of these early results.

Meanwhile, Medical News Today recently learned of another breakthrough where researchers show how two already approved antimalaria drugs may slow Parkinson's disease. In the Proceedings of the National Academy of Sciences, the international team explains how they screened 1,000 existing drugs and found two antimalaria drugs that improved movement control in rats with Parkinson's-like symptoms.

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