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Vitamin B1 pathway could hold malaria clue


Half of the world's population are at risk of malaria and resistance to anti-malarial drugs is a major problem (Source: BeauDamonRichardsGallery/iStockphoto)

Anti-malarial clue A new anti-malarial drug that stops the malaria parasite from using vitamin B1 is now plausible, say researchers.

Pharmacologist, Dr Kevin Saliba, from the Australian National University, and colleagues, report their findings in recent issue of Nature Communications.

"We can target the pathways by which the parasite takes up the vitamin and metabolises it," says Saliba. "These pathways can serve as drug targets."



Saliba and colleagues wondered whether it might be possible to inhibit this thiamine metabolism pathway.


To provide proof of principle they looked at what happens to the pathway involving two enzymes - oxoglutarate dehydrogenase and pyruvate dehydrogenase.


Saliba and colleagues also gave the thiamine analogue to mice infected with malaria and found they lost weight.

"That's consistent with the drug having some toxicity," says Saliba.

He says the thiamine analogue used here would interfere with energy metabolism in humans so any anti-malarial drug based on these findings would have to be designed very carefully.

"The idea is that you come up with a drug that would selectively target the parasite pathway," says Saliba. "We would have to rely on slight differences between the human and parasite thiamine metabolism pathways."

There are currently anti-malarial drugs that target folate metabolism, says Saliba, which means there is a precedent for having a drug that targets a metabolic pathway in a pathogen that also exists in humans.



"The malaria parasite has become resistant to just about all the drugs we've used against it," says Saliba.


"It will be more difficult for the parasites to become resistant to a drug that's binding to several enzymes," says Saliba.

About 3.3 billion people - almost half of the world's population - are at risk of malaria, according to the World Health Organization.

Tags: malaria