Natural products for the control of malariaMalar J. 2011 Mar 15;10 Suppl 1:S1
VIII. A “reverse pharmacology” approach for developing an anti-malarial phytomedicineWillcox ML, Graz B, Falquet J, Diakite C, Giani S, Diallo D
Malar J. 2011 Mar 15;10 Suppl 1:S8
PubMed Central PMCID: PMC3059466
Merlin L Willcox of the University of Oxford and Research Initiative for Traditional Antimalarial Methods, along with coauthors from the University of Geneva, Département de Médecine Traditionnelle (Mali) and Aidemet, describe a novel “reverse pharmacology” pathway for developing new antimalaria medicines from traditional herbal remedies.
From the abstract:
“A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.”
Noting that “conventional drug development is slow and expensive, taking up to 15 years and up to $800m to develop a new drug,” and that “the finished products are often unavailable and unaffordable to the poorest patients in remote areas, unless they are part of a heavily subsidized scheme,” the team hypothesized that development of standardized phytomedicines in parallel with conventional drug development might prove to be a faster, cheaper, and more sustainable approach for remote areas where malaria is endemic.
Reverse pharmacology was originally developed in India and China in the Mid-20th Century to make use of Ayurvedic and Traditional Chinese whole systems of medicine while at the same time employing the conventional pharmaceutical pathway of isolating compounds for further development.
The team developed and tested a reverse pharmacology pathway using a traditional herbal medicine derived from Argemone mexicana, a pan-tropical weed found in many places where malaria is endemic. In contrast to the conventional pharmaceutical pathway, the reverse pharmacology process took six years and cost about 400,000 Euros.
At the time of writing, the new antimalarial phytomedicine developed from the Argemone mexicana decoction was in the process of being approved in Mali.
The reverse pharmacology pathway had four discrete stages:
- Selection of a herbal remedy
- Dose-escalating clinical study
- Randomized controlled trial
- Isolation and testing of active compounds
In addition to the Argemone mexicana phytomedicine, the authors report that other phytomedicines for malaria have already been developed and are government-approved in Burkina Faso (Cochlospermum planchonii root decoction), in Ghana (Cryptolepis sanguinolenta root infusion) and in the Democratic Republic of Congo (Artemisia annua Anamed leaf infusion).
The authors recommend that funding organizations “support the possibility of developing new types of medicines, including phytomedicines, rather than restricting funding only to conventional development of isolated active compounds,” with sustainable public health improvement in remote areas as a key consideration.
Read the complete article at PubMed Central.
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