Promising drug candidate tackles malaria in a new way

20 Jul

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.

The new compound offers potentially long-lasting effects in preventing and treating


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


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


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


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


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.

Written by Catharine Paddock PhD

Copyright: Medical News Today