The discovery, published today in the journal ‘Nature’, came about through collaboration between the University of Dundee’s Drug Discovery Unit and the Medicines for Malaria Venture (MMV), which was supported by the Wellcome Trust.
The malaria parasite Plasmodium falciparum has developed resistance to many current drugs, meaning that new therapies are needed to overcome this problem. The compound identified by Professor Ian Gilbert and colleagues (called DDD107498) works by blocking protein synthesis within the parasite and is effective against multiple life cycles.
DDD107498 has been shown to be successful in mouse models of malaria and is now beginning preclinical development. The researchers estimate that a drug developed using the compound would cost around US$1 per treatment, which would make it affordable for patients living in low-income countries that are most severely affected by malaria.
Professor Ian Gilbert, Head of Chemistry at the Drug Discovery Unit, led the team that discovered the compound. He said: “The research published today reveals that DDD107498 has the potential to treat malaria with a single dose, prevent the spread of malaria from infected people and protect a person from developing the disease in the first place. There is still some way to go before the compound can be given to patients. However, we are very excited by the progress that we have made.”
Dr David Reddy, CEO of MMV, said: “Malaria continues to threaten almost half of the world’s population – the half that can least afford it. The collaboration to identify and progress the compound, led by the Drug Discovery Unit at the University of Dundee, drew on MMV’s network of scientists from Melbourne to San Diego. The publication of the research is an important step and a clear testament to the power of partnership.”
Dr Kevin Read, joint leader of the project and also based at the Drug Discovery Unit at Dundee, said: “New drugs are urgently needed to treat malaria, as resistance to the current gold-standard antimalarial drug is now considered a real threat. The compound we have discovered works in a different way to all other antimalarial medicines on the market or in clinical development, which means that it has great potential to work against current drug-resistant parasites. It targets part of the machinery that makes proteins within the parasite that causes malaria.”
Dr Michael Chew from the Wellcome Trust, which provides funding for the Drug Discovery Unit at Dundee and MMMV, added: “The need for new antimalarial drugs is more urgent than ever before, with emerging strains of the parasite now showing resistance against the best available drugs. These strains are already present at the Myanmar-Indian border and it’s a race against time to stop resistance spreading to the most vulnerable populations in Africa. The discovery of this new antimalarial agent, which has shown remarkable potency against multiple stages of the malaria lifecycle, is an exciting prospect in the hunt for viable new treatments.”
Image: Blood smear showing the presence of P. falciparum parasites in the red blood cells. Credit: Spike Walker/Wellcome Images.
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Baragana et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature doi:10.1038/nature14451