BioEd Online

After more than a decade of research, scientists believe they have come up with a fresh line of defence against the increasingly drug-resistant malaria parasite. Results suggest that the drug, which recently entered clinical trials in Britain, could revolutionize treatment of the disease.

Malaria claims around 1 million lives every year, and causes a further 300 million people to fall sick. In both Africa and Asia, the malaria parasite (Plasmodium falciparum) is becoming resistant to drugs such as chloroquine, which has been a staple of malaria treatment since the 1960s.

More recently, drugs based on the traditional Chinese remedy artemisinin have been developed. They are effective against chloroquine-resistant strains of parasite. But they can be expensive for developing nations and patients often find it difficult to stick to the weeklong course of treatment.

The new medicine, called RBx-11160, is a synthetic, slightly altered version of artemisinin. It only needs to be taken for around three days, and its simple structure means it should be at least five times cheaper to produce. Its development is reported in Nature this week¹.

Yuanqing Tang from the University of Nebraska Medical Center, Omaha, helped to develop the drug and is excited by its prospects. "We hope RBx-11160 will prove useful for treating drug-resistant strains of the disease," he says.

Chemical warhead

Artemisinin-based drugs contain a hidden antimalarial warhead: a chemical bridge made of oxygen atoms. When the bridge is ruptured inside the parasite's gut, toxic free radicals are released and the microbe is destroyed.

Tang and colleagues have produced an altered version of the molecule that contains extra chemical groups to make the drug soluble in water and more stable.

Better solubility means the drug can be given orally or injected intravenously. Added stability means that less of the compound is broken down as it travels to the blood plasma, where the parasite lives.

The new version is also more potent. When infected mice are given the drug, 95-100% of parasites disappear within four days. Conventional artemisinin drugs take a week to clear 95% of parasites.

Trial runs

The drug entered preliminary human safety trials in Britain last month. "Initial results are promising," says Tang, but he cautions that it will be some time before the full data are available.

"This is potentially extremely important," says malaria researcher Paul O'Neill from Liverpool University, UK. If the drug works well in people, it would probably be given in combination with a second drug, which would kill any parasites missed by RBx-11160.

As well as curing patients, this strategy would minimize the development of drug-resistant strains. "The parasites find it more difficult to develop resistance when bombarded by two drugs targeting multiple pathways," says O'Neill.

The development of RBx-11160 is a flagship project for the Medicines for Malaria Venture, a non-profit organization that aims to encourage the development of affordable antimalarial drugs by bringing together academic researchers and private companies.

Three academic groups and three biotechnology firms collaborated to produce RBx-11160. "It is an excellent example of how a well managed partnership can have a significant impact on antimalarial product research and development," says O'Neill.