Semi-synthetic shortcut could boost supply of antimalarial
pharmafile | July 15, 2010 | News story | Manufacturing and Production |Â Â malariaÂ
US researchers are pushing forward with the development of a cheaper, semi-synthetic version of artemisinin, the basis of the most effective treatment for malaria currently available, with the help of $10.7 million in funding from the Bill & Melinda Gates Foundation.
Artemisinin-based combination therapy (ACT) is the mainstay of malaria treatment at the moment because it is largely free of the resistance seen with older drugs, particularly among the most virulent strains of the Plasmodium falciparum malaria parasite.
At present artemisinin is derived from the sweet wormwood plant (Artemisia annua), and extracting the active ingredient from the material is a fairly arduous and expensive process. The new version is made in genetically-engineered bacteria developed by scientists at the University of California-Berkeley.
The UCB team, led by Jay Keasling, used a technique for transplanting yeast and plant genes into bacteria to construct an entirely new metabolic pathway inside one bacterial strain that can be used as precursors for a number of plant-derived chemicals, including artemisinin.
A semi-synthetic supply of the drug would be invaluable as it will help smooth out the peaks and troughs in the cost of bulk ingredient. Artemisinin’s cost per kilo has fluctuated from a low of around $150 in 2008 to over $400 today, and is unreliable because much of the crop is grown by small farmers. If prices dip too far, farmers sometimes swap over to more lucrative crops and create shortages.
Further development of the semi-synthetic artemisinin is being carried out by non-profit pharmaceutical company the Institute for One World Health (iOWH), in partnership with multinational drugmaker Sanofi-Aventis, and the hope is to have ACTs based on the ingredient on the market in 2012.
iOWH, UCB and a company co-founded by Keasling called Amyris came up with the original process in 2004, with Sanofi-Aventis coming on board in 2008 to help scale it up. From the artemisinin molecule it is possible to synthesise derivatives, such as artesunate and artemether, which form the basis of the ACT regimens in use today.
“We are confident that the semi-synthetic artemisinin production processes will improve the availability of high-quality artemisinin derivatives to drug manufacturers,” commented Jack Newman, a co-inventor of the production technology and co-founder of Amyris.
With commercial scale production just over the horizon, “millions of people infected with malaria [will be able] to gain access to lifesaving treatments,” he added.
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