Scientists believe they have unlocked the workings of an ancient Chinese herbal remedy which has become one of the brightest yet most puzzling hopes in the war against malaria.
The knowledge, they hope, may give rise to a new generation of cheaper, more effective drugs against a scourge that kills around a million people each year and infects hundreds of millions more.
”We are particularly pleased to have found the missing piece in the anti-malarial jigsaw and solved one of the longest-running mysteries about how a critical anti-malarial works,” the researchers said in a statement on Wednesday, on the eve of the
publication of their work.
”We cannot wait to apply this information in areas where there is a lot of drug resistance in (malaria) parasites.”
The remarkable story behind the herb starts off in 340 AD, when a Taoist scribe wrote Zhou Hou Bei Ji Feng (Handbook of Prescriptions for Emergency Treatments), giving a recipe for using sweet wormwood (qing hao) in an infusion for treating fever.
More than 1 200 years later, a Chinese sage, Li Shizen, realised that this could be used for tackling the symptoms of malaria, and included the treatment in a compendium that is a landmark in Chinese medical history.
There things lay until 1972, when Chinese scientists took an interest in the plant’s reputed qualities. They successfully extracted the plant’s active compound, calling
it qing hao su — transcribed into artemisinin in conventional scientific terminology, after the herb’s Latin name, Artemisia annua.
Artemisinin has since become a leading medication against the malaria parasite, not least in Southeast Asia, where the cheapest frontline treatments, chloroquine and sulphadoxine-pyrimethamine, are encountering big resistance problems.
But how artemisinin works has never been clear.
The prevailing theory was that it interacts with haem molecules, the iron-rich debris from red bloodcells which are destroyed by the parasite as it replicates around the body.
This interaction then unleashes massive quantities of free radicals –atoms with unpaired electrons which are linked with cell death — which go on to kill the parasite, according to this thinking.
But years-long research led by Sanjeev Krishna of St. George’s Hospital Medical School in London concludes that artemisinin takes a quite different path.
Artemisinin, they found, works by blocking the action of a metabolic enzyme called PfATP6 that is vital for ”pumping” calcium in and out of the parasite’s cells.
All complex cells need calcium ”pumps” to drive their molecular motors.
Krishna’s team, which infected frogs’ eggs with the enzyme and exposed them to artemisinin and a conventional rival, believe that PfATP6 is exclusive to the malaria bug as the activator of its ”pump”.
If this is confirmed by more biochemical evidence, rather than by observation alone, that opens an exciting new target against the parasite and one that is far less prone to mutation, which is the source of drug resistance.
And it also throws up the possibility of synthesising cheap drugs that, like a sniper’s bullet, specifically shut down the parasite’s calcium ”pump” but have no effect on anything else in the body.
”PfATP6 is… now a prospective target for the development of new antimalarial drugs,” World Health Organisation (WHO) tropical disease expert Robert Ridley says.
”(…) The ever-growing threat of resistance to antimalarial drugs gives the work of Krishna and colleagues a practical significance beyond its undoubted academic merit.”
The study and commentary are published on Thursday in Nature, the British science weekly. – Sapa-AFP