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DRUGS & PHARMACROPS: Genetically modified chicory brings hope toAfrican malaria patients

------------------------------- GENET-news -------------------------------
TITLE:  Genetically modified chicory brings hope to African malaria
SOURCE: Plant Research International, The Netherlands
AUTHOR: Press Release
DATE:   08.05.2007

Genetically modified chicory brings hope to African malaria patients

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.

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