Paris - 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."
Artemisinin has since become a leading medication
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 Natoms with
unpaired electrons which are linked with cell death N 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
