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European Commission funded research leads to effective new malaria drug
December 13, 2002In an article published in the latest issue of The Lancet 1) , an international consortium, funded by a EUR1.8 million research grant from the European Commission, reports successful efficacy trials of a new candidate drug against malaria. If these initial results are confirmed a new drug could be available within 3 years. This raises new hopes in the combat against poverty-linked diseases, in particular in the face of the resurgence of drug-resistant forms of malaria in areas where it was though to have been eradicated.
Malaria is endemic in tropical and subtropical regions, with sub-Saharan Africa, South Asia and South America being particularly affected. Every year 1.5 to 3 million humans die from malaria and the majority of these are children under 6 years. Recently, the disease returned to areas where it was eradicated decades ago. Moreover, first cases of malaria are reported from areas that were considered malaria-free in the past, such as central Asia and Eastern Europe. Consequently, today more people die from malaria than 30 years ago. The most important reason for this is the spread of malaria parasites that are resistant to current drugs. Thus, there is an urgent need for development of new malaria drugs.
A novel approach
This is the first time that the active compound fosmidomycin has been used for the treatment of malaria in humans. It is a good example of the rapid exploitation of genomic information for clinical applications. The therapeutic principle was developed by biotechnology company Jomaa Pharmaka GmbH in co-operation with the University of Giessen, Germany2) , and it was further developed to clinical application by a European Commission funded research consortium involving the following partners: Université Louis Pasteur (France), Hôpital Albert Schweitzer (Gabon), Organisation de Lutte Contre les Endémies en Afrique Centrale (Cameroon), Biomedical Primate Research Centre (Netherlands), Universidad del Valle (Colombia), and Universidade de S'£o Paulo (Brazil).
How it works
Fosmidomycin inhibits an enzyme crucial for the malarial parasite: 1-deoxy-D-xylulose-5-phosphate (DOXP) reductoisomerase. This enzyme is involved in the biosynthesis of certain vital biomolecules, the so-called isoprenoids. In humans, these substances are produced via a biochemical pathway different to that of malarial parasites, so it is not toxic for humans.
Proven efficacy
The novel compound proves to be a highly effective drug against malaria. In a clinical study conducted on 27 patients at the Albert Schweitzer hospital in Lambaréné (Gabon), a team of scientists under the direction of Prof. Peter Kremsner of the University of Tübingen demonstrated that fosmidomycin readily kills the malaria parasite Plasmodium falciparum. The full results are published in the medical journal "The Lancet" dated 14 December1.
The founder of Jomaa Pharmaka, Dr Hassan Jomaa, considers fosmidomycin an important innovation for the fight of severe malaria cases, as it is one of the few substances in recent years with a completely novel mode of action. In the region of Lambaréné, practically all malaria parasites are already resistant to chloroquine, and at least 30 per cent against sulfadoxine/pyrimethamine. Yet, fosmidomycin is also effective against these multi-resistant strains, says Dr Jomaa.
Future developments
It will take approximately three more years until the new drug can be made commercially available. In the meantime, a combination of fosmidomycin with another anti-malarial compound will be tested with a view to shorten the duration of therapy, and prevent the emergence of resistances. First clinical studies on a combination therapy are already being performed. As the new drug is well tolerated, it will be especially valuable for the treatment of children with malaria.
The fight against poverty-linked diseases
This advance made through this project entitled "Clinical and pre-clinical evaluation of fosmidomycin and its derivatives as antimalarial drugs", which obtained a EUR1.8 million research grant from the European Commission's INCO programme, provides encouragement for European Commission-led efforts to combat poverty-linked infectious diseases.
Earlier this year the European Commission proposed to support a long-term partnership between Europe and developing countries by providing EUR200 million for the development of new medicines and vaccines against HIV/AIDS, malaria and tuberculosis. This European and Developing Countries Clinical Trials Partnership (EDCTP) brings together the EU Member States plus Norway, developing countries and industry in a joint effort to combat poverty-linked diseases.
"European research is at the forefront in the fight against poverty-related diseases", said European Research Commissioner Philippe Busquin. "We plan to invest EUR400 million in research against malaria, tuberculosis and AIDS over the next four years. Half of this will serve to fund clinical research in co-operation with developing countries and industry through a shared platform with European countries that will pool a total budget of EUR600 million. Scientists already work together internationally. Now we also need governments and other donors to structure their research and development investments."
European Commission, Research Directorate
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