Malaria drugs may get new lease of life
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by Maore Ithula Researchers have isolated how the malaria parasite resists the otherwise effective and cheap drug chloroquine. Reporting their findings in the journal Science, Biochemist Rowena Martin and colleagues at the Australian National University in Canberra, say it is now possible to stop the resistance, at least in the laboratory.The researchers say this knowledge will help in the development of new chloroquine-like drugs capable of evading the effect of the gene PfCRT. Scientists implicate the gene in the parasites resistance to chloroquien. To understand how the researchers made the discovery, it is important to understand how chloroquine worked before the parasite mutated to strains that resist treatment. Dr Elizabeth Juma, head of the Division of Malaria Control at the Ministry of Health, says when a malaria parasite invades the human blood cell it feeds on the haemoglobin protein, breaking it up into amino acids. The haemoglobin protein is the red component of the red blood cells. This process, says Juma, produces a toxic iron waste product that could kill the parasite. However, the parasite converts the dead waste into a harmless inert crystal, and stores in its stomach. Toxic iron Chloroquine works by stopping this protective conversion of iron waste, causing toxic iron to build up in the parasite’s stomach, she says. The parasite is killed by its own waste product, says Juma. In 2000, there was a breakthrough, which implicated PfCRT in malarial resistance to chloroquine. But no one quite knew how the PfCRT protein caused resistance, notes the report published online in Science. To study PfCRT’s function, without the interference of other factors in the malaria parasite, Martin and colleagues developed a new laboratory system, which isolated the chloroquine-fighting protein in an unfertilised frog egg. "We had a nice clean slate and can throw anything we like at it and see what happens," said Martin, whose research was funded by Australia’s National Health and Medical Research Council. The researchers demonstrated that PfCRT allowed chloroquine to leak out of the parasite’s stomach, preventing it from reaching the concentrations it needed to work. "The protein provides an exit route for chloroquine," said Martin. Martin says this knowledge will help in the development of new chloroquine-like drugs that will be capable of evading the effect of PfCRT and won’t leak out of the parasite’s stomach. The scholars tested a resistance reversing drug and showed that it actually blocked the chloroquine exit route. Side effects However Juma says there is nothing new in the findings and that the resistance could have more devastating side effects because it can also block other systems of the body. In the report, Martin concedes countering drug resistance is a constant battle. "It is a little inevitable the pathogen will catch up eventually," she says. "Chloroquine really changed malaria treatment and it’s estimated to have saved more lives than any other drug in history, says Martin. But since the drug was introduced in the 1930s, she says the malaria parasite has been slowly building resistance to it and in some areas of the world the drug is totally ineffective. "Now we’re actually pretty much down to a handful of drugs and those drugs are all quite expensive," Martin said. Martin says "funky" drugs could be made that fuse chloroquine with "resistance reversing" chemicals, which are known to stop PfCRT’s effects.