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Dafra Pharma International NV has commissioned Plant Research International
(PRI) to start new research to optimize the production method of artemisinin
via genetically modified chicory plants.
This research should result in inexpensive, large-scale production of
artemisinin under controllable conditions. Artemisinin is a basic raw
material used in ACTs (Artemisinin based Combination Therapies), the latest
generation and most effective antimalaria treatment according to the WHO
(World Health Organization of the UN).

Dafra Pharma International NV, private market leader in ACTs in Africa,
wants to use the results of this research to lower the price of the basic
raw material to such an extent that its treatments of the African patient
will soon cost no more than half a dollar.

Malaria and ACTs
According to the WHO some 300 to 500 million malaria cases are reported
annually worldwide. Each year this results in the death of 1.5 to 2 million
people, of which 90% occur in Africa. Malaria is the main cause of death in
most African countries, more than HIV/Aids. The disease is in particular
fatal for pregnant women (10 000 per year) and young children (3000 per
day). Each 30 seconds a child under five dies of malaria in Africa.

And yet malaria is perfectly treatable. Rapid diagnosis and treatment with
an ACT can cure a patient before the disease becomes life-threatening. Since
the malaria parasite has become resistant to the older, more conventional
antimalaria treatments such as chloroquine, SP etc., the WHO recommends ACTs
as the first-line treatment in the African countries. Artemisinin, however,
is an expensive plant extract. This means that an ACT these days easily
costs ten times more than a treatment with e.g. chloroquine. ACTs are very
expensive for the African patients. This means that the price of the ACTs,
and thus the price of artemisinin, needs to drop sharply.

Biosynthetic production of artemisinin via plants
The idea of producing molecules via genetic modification is not new. Based
on a Dutch patent Prof. Jay Keasling (Berkely University, California, USA) &
One World Health already made the first steps in the biosynthetic production
of a precursor of artemisinin. They introduced the genetic information for
production of artemisinic acid (obtained from Artemisia annua) in yeast. Via
genetic modification of microorganisms and via fermentation they hope to
produce artemisinic acid on an industrial scale.

Earlier research by Plant Research International, commissioned by Dafra
Pharma International NV, followed a different path along the same lines of
thought, though not using microorganisms, but plants. The Wageningen
research showed that chicory produces considerable amounts of sesquiterpene
lactones which give the plant its bitter taste. The Wageningen scientists,
headed by Prof. Harro Bouwmeester and Dr. Maurice Franssen, could
demonstrate that the enzymes that in chicory are involved in the production
of the bitter compounds are also capable of performing other reactions. Via
a diversion of the biosynthesis of bitter compounds they intend to produce
the chemical precursor for artemisinin (dihydroartemisinic acid) in the
roots of chicory. The group of Prof. Bouwmeester has shown in a wide range
of plant species that diversion of the biosynthesis of terpenes can be
carried out very efficiently.

New research of Plant Research International, also for Dafra Pharma
International NV, is now being initiated to see how the precursor of
artemisinin can best be produced in chicory. Dafra Pharma International NV
has the chemical expertise required for the conversion, after extraction,
of the precursor into artemisinin that is directly suitable for the
production of ACTs.

The Belgian-Netherlands research will run parallel with that of Prof.
Keasling in the USA. In fact both studies are complementary, with the same
human objective: the large-scale production of a biosynthetically produced
artemisinin which should lead to inexpensive, but high-quality, effective
and safe antimalaria treatments (ACTs) for Africa.

Industrial scaling up for humane cause
To free Africa from malaria ? the slogan of World Malaria Day 2007 ? some
400 million treatments per year will be needed. Plant Research International
and Dafra Pharma International NV will therefore continue their close
cooperation in the optimization of the biosynthesis technology for the
industrial production of artemisinin.

In the context of this cooperation a patent assigned to Plant Research
International will be sold to Dafra Pharma International NV. This will allow
the use of the knowledge acquired by Plant Research International in a
product-oriented process.

Plant Research International and Dafra Pharma International have chosen
inulin chicory as artemisinin production platform because it contains some
essential precursors and enzymes and is a well-established industrial crop
for a.o. non-food applications, which means that the entire chain of
large-scale agricultural production, including extraction, is already
present, in Belgium as well as in the Netherlands.

Dr FH Jansen, R&D Director of Dafra Pharma International NV, states that it
must be the objective of Dafra Pharma International NV to achieve
inexpensive, large-scale industrial production of artemisinin under
controllable conditions via the root of the chicory plant in three to five
years time.

In the future this new inexpensive raw material should enable Dafra Pharma
International NV to place its ACTs on the market for half a dollar per adult
antimalarial treatment.

[www.pri.wur.nl]