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Genetically modified chicory brings hope to African malaria patients

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Wageningen, The Netherlands
May 8, 2007

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.

Dafra Pharma International NV is a Belgian pharmaceutical company founded 10 years ago by Mr Bruno Jansen. The company is private-sector market leader in all Africa for Artemisinin-based Combination Therapies to cure malaria.
Since its founding Dafra Pharma International NV has focused on the development of and research into medications for "neglected tropical diseases" such as malaria, sleeping sickness, schistosomiasis, TBC, leishmaniasis, etc.
Dafra Pharma International NV has over the years built a unique distribution and promotional network in Africa (36 countries) with now already more than 120 local African medical representatives.

Plant Research International is part of Wageningen UR and is the most important Netherlands research institute for scientific research on plants. The institute combines knowledge and experience in scientific fields like genetics and reproduction, genomics, proteomics, metabolomics, bioinformatics, crop protection, crop ecology and agrosystems, offering a unique range of perspectives for government and industry.
The institute develops and uses genetic modification for research on sustainable agriculture, healthy food and a safe environment.

The Plant Sciences Group of Wageningen UR is a collaboration of:
- Plant Research International B.V.
- Applied Plant Research (Praktijkonderzoek Plant & Omgeving B.V.)
- Wageningen University

 

 

 

 

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