14 May 2008, 17:39
by Elspeth Bartlet
The aromatic herb Artemisia is the sole source of artemisinin, which is the essential ingredient of WHO-recommended treatments for malaria. Diversification is the key to improving quality sources of artemisinin supplies, hence stabilizing the market and making ACTs more affordable. The Artemisinin Enterprise is a collaboration of three projects seeking new sources of artemisinin and antimalarial compounds.
Artemisinin-based combination therapies (ACTs) are recommended by the World Health Organization as the most effective treatments for malaria and have been adopted as policy by most countries in Africa and Asia. However, actual deployment of these medicines to malaria sufferers has been slow. A major barrier to their uptake is cost: ACTs are many times more expensive than the drugs they are replacing (such as chloroquine). Both government programmes and parents of children with malaria struggle to pay for ACT drugs, compounded by the fact that children under five often suffer from malaria multiple times each year.
A significant driver of these high prices is the cost of artemisinin production: artemisinin derivatives can account for 35-70% of manufacturing costs (depending on formulation and co-ingredient). Artemisinin is derived from the medicinal plant Artemisia annua, but the plant only produces tiny amounts, which makes artemisinin expensive to produce. The situation is made worse by uneven supplies which have caused prices to fluctuate from US$250-1700/kg in recent years. Variable quality is an additional problem.
READ ON: Ensuring sustained ACT production and reliable artemisinin supply. Jean-Marie Kindermans, Jacques Pilloy, Piero Olliaro and Melba Gomes: Malaria Journal 2007. 6:125
Three organizations with support from the Bill & Melinda Gates Foundation have formed the Artemisinin Enterprise, an advocacy coalition of R&D projects developing new and diverse methods for producing high quality artemisinin. Together, these strategies will stabilize the supply and diversify the sources of high quality artemisinin, lower the cost of artemisinin production and develop new antimalarial combinations; making ACTs accessible to far more of the people who need them.
The Artemisinin Enterprise comprises:
- A collaboration led by Institute for OneWorld Health (iOWH) to develop semisynthetic artemisinin through fermentation;
- The Centre for Novel Agricultural Products (CNAP) of the University of York, which is applying fast-track breeding technologies to develop new, high-yielding varieties of Artemisia annua plant;
- The Medicines for Malaria Venture (MMV), working on novel therapies for treatment of malaria.
Semisynthetic artemisinin through fermentation
READ ON: The Institute for OneWorld Health
A partnership of the Institute for OneWorld Health, University of California, Berkeley, Amyris, and sanofi-aventis called the Artemisinin Project, is using synthetic biology and classic chemistry techniques to develop semisynthetic artemisinin.
READ ON: Victoria Hale, Jay D. Keasling, Neil Renninger, and Thierry T. Diagana. Microbially Derived Artemisinin: A Biotechnology Solution to the Global Problem of Access to Affordable Antimalarial Drugs, Am J Trop Med Hyg, Dec 2007; 77: 198 – 202
Over the course of the grant, the project aims to create, optimize, scale-up, and industrialize microbial production systems to make bulk artemisinin available for incorporation into ACTs, at a low price with consistent high quality.
A second source of artemisinin, in addition to plant-derived material, is needed to ensure global supply needs can be fulfilled due to current market volatility. If technical benchmarks are achieved, the project would progress to the commercial manufacturing phase with the goal to facilitate integration of semisynthetic artemisinin into the supply chain and ACTs by 2010.
Fast-track breeding of Artemisia
The Centre for Novel Agricultural Products at the University of York is using the latest genetic technologies to fast-track the plant breeding of Artemisia and increase plant output. “This plant is little changed from its weedy origins and there is a lot of scope for improvement” explains project leader Dianna Bowles. “If we can double the plant’s yield of artemisinin, we will half the costs of cultivation and extraction”.
Thousands of plants are being screened for their artemisinin content and other useful features. This screening of traits is backed up by DNA screening that can pick out plants with the genetic potential to improve yield. Plants selected by this process will be used to breed new high-yielding, non-GM plant varieties. The project has adopted a non-GM strategy in order to minimise the regulatory burden the novel varieties will face.
A new class of synthetic peroxides
READ ON: Medicines for malaria venture
The artemisinin molecule contains a peroxide chemical bond, which is believed to be essential to its anti-malarial activity. The not-for-profit organization Medicines for Malaria Venture (MMV) is collaborating with a number of research partners including the University of Nebraska, Monash University, and the Swiss Tropical Institute, on the development of a new class of antimalarial compounds, dubbed the “Next Generation OZ” compounds, that have a similar peroxide moiety.
“The OZ team is now testing these next generation compounds to find drug candidates that could potentially have different properties to artemisinin,” said Ian Bathurst, Director Drug Discovery and Technology, MMV. “The goal is to find an alternative to current artemisinin-derived drugs that will be cheaper and more effective. We already have a single-dose cure in an animal model and are now planning to run a clinical trial in humans.”
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