Scientists Describe Breakthrough in Anti-Malarial Precurser

Scientists from Amyris published in the journal Nature the details of a major breakthrough in the field of synthetic biology that allows for the production of a key precursor to Artemisinin, the key ingredient in the world’s most effective and preferred drug in combating malaria. Earlier today, pharmaceutical company Sanofi announced the launch of large-scale industrial production of Artemisinin utilizing Amyris designed strains.

“Yesterday, a group of scientists led by Amyris detailed how we engineered simple baker’s yeast strains to produce unprecedented concentrations of the precursor to the anti-malarial drug ingredient. Today, Amyris scientists celebrate Sanofi’s successful launch of the industrial production of the world’s first semi-synthetic Artemisinin utilizing Amyris designed strains,” said John Melo, President & Chief Executive Officer of Amyris.

“Sanofi’s commercial launch of this key precursor to life-saving drugs produced with our technology underscores not only the success of Amyris’s synthetic biology platform at scale but also the positive impact this technology can have on our planet,” Melo concluded.

Malaria is a preventable disease that affects over a quarter of a billion people and claims the lives of 650,000 people annually, mostly children under the age of five in Africa. Artemisinin, sourced from the wormwood plant, Artemisia annua, has been used for centuries in treating malaria but its availability, cost and quality have been highly volatile.

Working with a number of partners, and with generous support from the Bill & Melinda Gates Foundation via OneWorld Health (now PATH’s Drug Development Program), Amyris developed technology to convert plant-sugars into Artemisinic Acid, a late stage precursor to the anti-malarial drug ingredient, Artemisinin. The details of this breakthrough process, as well as an alternative process for converting Artemisinic Acid into Artemisinin, can be found in the online publication of the scientific journal Nature.

In 2008, as part of this non-profit project, Amyris made available its Artemisinic Acid-producing yeast strains to Sanofi, via OneWorld Health, on a royalty-free basis. As separately announced by Sanofi earlier today, this technology is now being used at large-scale to produce Artemisinin, which will be combined in pill form with another anti-malarial in what is called Artemisinin-based Combination Therapy (ACT). Sanofi has indicated it plans to produce enough semi-synthetic Artemisinin for up to 150 million ACT treatments by 2014 and will ensure its distribution under the “no profit, no loss” principle.

“Amyris technology will alleviate drug manufacturers’ dependency on erratic supply of plant-derived Artemisinin and reduce costs to malaria patients. This non-profit project is at the core of Amyris’s values and culture, born from a passion to make a positive impact in the world through science,” said Jack Newman, Amyris co-founder and Chief Scientific Officer.

Source: Amyris

Canadian Researchers Develop Inexpensive Malaria Treatment

Scientists in Saskatoon, Canada have developed a malaria treatment that will help fight malaria, which kills about one million people each year.

The new developments which will provide an affordable, reliable, and stable treatment for malaria and is likely to save millions of lives, especially those of women and children in Africa. The Honourable Gary Goodyear, Minister of State for Science and Technology, along with Mr. Brad Trost, Member of Parliament for Saskatoon–Humboldt, announced the breakthrough today and highlighted the Government’s research support.

“Our government is committed to improving the health of women and children in developing countries,” said Minister Goodyear. “This new development in the production of a malaria treatment represents a major development in the fight against the disease. It will strengthen Canada’s position as a world leader in health research and provide a reliable and affordable solution.”

Today’s announcement is a result of  The Artemisinin Project, a public-private partnership led by OneWorld Health in collaboration with sanofi-aventis, Amyris, the University of California at Berkeley, and the National Research Council Canada. Artemisinin is a natural compound found in a traditional Chinese medicinal plant grown mainly in Africa and Asia to treat malaria. The Government of Canada’s investment of approximately $869,000 in this research has led to technology that can produce a stable and affordable supply of artemisinin for the developing world on a not-for-profit basis.

“Collaboration on the development of this new technology promises to have a major impact on supply of malaria treatment across the developing world, which will be an important contribution towards the global effort to combat malaria,” said Dr. Richard Chin, Chief Executive Officer of OneWorld Health.

According to the World Health Organization, malaria causes approximately 250 million illnesses and more than one million deaths each year, of which 90 percent occur in Africa, mostly in pregnant women and in children. The disease is endemic in nearly 100 countries, including 28 on the African continent. This project is expected to help treat 200 million cases and prevent over one million deaths annually.

About the National Research Council of Canada’s Artemisinin Research

In 2003, researchers at the National Research Council of Canada (NRC) in Saskatoon set out to identify the genes that control the synthesis of artemisinin. Produced by Artemisia annua (a traditional Chinese medicinal plant), this natural compound is extracted from plants grown in Africa and Asia to treat malaria — a major threat to maternal and child health around the world.

Led by Dr. Patrick Covello, the NRC team identified various genes in the plant’s metabolic pathway that produce artemisinin. Using various microbial and plant platforms, such as yeast and tobacco, they conducted research to find alternative means of supplying low cost artemisinin-based drugs.

The Government of Canada has invested approximately $869,000 in this research. In partnership with Amyris, OneWorld Health and sanofi-aventis, NRC’s technology promises to have a major impact on malaria treatment across the developing world.

The NRC worked in partnership with “The Artemisinin Project,” funded by the Bill & Melinda Gates Foundation. This project is led by OneWorld Health, in collaboration with Amyris Biotechnologies, the University of California at Berkeley, and sanofi-aventis.

In 2004, the Institute for OneWorld Health was awarded $42.6 million from the Bill & Melinda Gates Foundation to develop a new source of artemisinin for distribution to the developing world. OneWorld Health created a collaboration between researchers at the University of California, Berkeley who were using yeast to synthesize high-value natural compounds produced by higher plants and other organisms. This work led to the creation of Amyris, a spin-off company, who also joined the collaboration. The aim of the Artemisinin Project was to identify genes in the artemisinin pathway and develop yeast strains that could produce large amounts of artemisinic acid, a key intermediate for the synthesis of artemisinin.

In 2008, the NRC and Amyris signed a license agreement, allowing the company to incorporate NRC’s discovery of two key genes in the artemisinin pathway into Amyris’ proprietary system, effectively doubling the yield of the end-product.

Subsequent to these research milestones, in July 2010, OneWorld Health announced an additional grant of $10.7 million from the Bill & Melinda Gates Foundation to scale-up production and commercialize the drug. Global pharmaceutical company, sanofi-aventis, is the partner that will formulate the drug for distribution on a not-for-profit basis across Africa and other regions vulnerable to the disease.

About Malaria

Malaria is a life-threatening parasitic disease transmitted by infected mosquitoes. Its symptoms include extreme exhaustion, fits of high fever, sweating, shaking chills and anemia.

Malaria parasites destroy red blood cells in the body, leading to anemia. Without adequate treatment, infected red blood cells block vessels leading to the brain or damage other vital organs, often resulting in death.

Infected people living in highly endemic areas often develop immunity to the disease and become asymptomatic carriers of malaria, contributing to epidemics.

According to the World Health Organization, malaria causes approximately 250 million illnesses and more than one million deaths per year, of which 90 percent occur in Sub-Saharan Africa. Malaria is endemic in nearly 100 countries, including 28 countries on the African continent.

In many countries, malaria is the leading killer of children under 5 years of age. Many children who survive an episode of severe malaria suffer learning impairments or brain damage.

Pregnant women and their unborn children are particularly vulnerable to malaria. More than 45 million women — 30 million in Africa — become pregnant in malaria-endemic areas each year.

During pregnancy, malaria can cause maternal anemia, impaired fetal growth, spontaneous abortion, stillbirth, premature birth and low birth weight. In sub-Saharan Africa, up to 40 percent of low birth weight is due to maternal malaria, resulting in up to 400,000 infant deaths per year.

In many areas, the malaria parasite is increasingly resistant to older, inexpensive, single drugs such as chloroquine. Currently, the most effective treatments involve combinations of artemisinin-based therapies and other antimalarials to prolong each drug’s effectiveness and delay resistance.

The source of artemisinin — Artemisia annua (also known as wormwood) — is cultivated mainly in Africa and Asia. However, because of the agricultural time scale, the delay between increased demand and new supply can be up to 14 months, causing shortages and limiting the ability to control the disease.

Source: National Research Council Canada