Malaria: the wizard of oz

The ancient Chinese pharmacopoeia has bequeathed Western medicine a dragon-slaying drug that promises to save the lives of up to two million people a year – half of them children under the age of two – in regions of the world haunted by drug-resistant strains of malaria.

The international research journal Nature today published news of the development of a potent new, synthetic anti-malarial drug derived from the ancient Chinese fever remedy, sweet wormwood (Artemisia annua).

The drug-synthesis project involved an international research team from the University of Nebraska, Monash University’s Victorian College of Pharmacy, the Swiss Tropical Institute in Basle, Switzerland, and three drug companies – Switzerland’s Hoffman La Roche, Fulcrum Pharma Developments in Hertfordshire, UK, and Basilica Pharmaceuticals in Basel.

Although the Chinese have used Artemisia as a fever remedy for more than 1500 years, the deadly malaria parasite Plasmodium falciparum has never evolved resistance to its active ingredient, artemisinin – even though the parasite has defeated all other anti-malarial drug thrown against it in the past two centuries, including quinine and chloroqine.

The new drug has been dubbed ‘Oz’, an abbreviation of ‘ozonide’. The parasite dies from the toxic effects of highly reactive ozone radicals spawned by a chemical reaction involving the iron-rich haem molecule in haemoglobin in red blood cells. The ozone molecules damage an enzyme critical the parasite’s survival in red blood cells.

Like artesunate and artemether, two other very effective semi-synthetic drugs, the new molecule harnesses the artemisin molecule’s ozone-generating “warhead”, an unusual structural feature called an endoperoxide bridge.

Synthetic chemists devised a chemical scaffold that not only stabilises the endoperoxidase bridge to prolong its killing activity, but actually makes it much more potent than other artemisinin derivatives.

Dr Bill Charman, of the Victorian College of Pharmacy, says the big advantage of the new synthetic drug over semi-synthetic artesunate and artemether is that the synthesis is simple, so it can be manufactured easily and cheaply.

The high cost of extracting artemisin from sweet wormwood and modifying it to make artesunate and artemether has prevented these drugs being used to treat chloroquine-resistant malaria in developing nations, particularly in Africa.

Charman said the research team’s major goal when it began the quest for a cheap, effective, low-toxicity drug for drug-resistant malaria was to ensure it would be affordable for even the poorest of nations – particularly in sub-Saharan Africa, where, on average, one infant dies every 30 seconds from drug-resistant malaria.

The new drug is expected to cost only $1 a day, and experiments indicate that three consecutive daily doses will completely clear a drug-resistant falciparum malaria infection. On this basis, it would cost a maximum of only $6 million a year to save 2 million lives.

The new drug is now entering clinical trials in Europe and Charman said that if all goes well, it could be in clinical use within three years.