ARCHIVED - NRC research underpins sustainable supply of anti-malaria drug

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May 10, 2011

NRC expertise in plant biotechnology will soon help provide an affordable and reliable treatment for malaria that could save millions of lives, especially those of women and children in Africa.

Under a public-private partnership funded by a $42.6 million grant from the Bill & Melinda Gates Foundation, several organizations including NRC have developed a novel source of artemisinin — a natural plant compound from which drugs are derived that kill the malaria parasite.

Artemisinin is produced by a traditional Chinese medicinal plant, called Artemisia annua, grown in Africa and Asia.

Artemisinin is produced by a traditional Chinese medicinal plant, called Artemisia annua, grown in Africa and Asia.

In 2004, the Institute for OneWorldHealth in South San Francisco partnered with the University of California at Berkeley (UC Berkeley) and its spin-off firm, Amyris, to work on an affordable and sustainable source of artemisinin. UC Berkeley’s aim was to identify the genes that control the synthesis of artemisinic acid, a compound that can be converted chemically to artemisinin and related drugs. Amyris’ aim was to achieve commercial levels of production using its proprietary yeast technology platform.

The PhytoMetaSyn project

Dr. Patrick Covello and his colleagues are now applying the expertise gained from the artemisinin project as part of a four-year $13.6-million research initiative funded by Genome Canada and other organizations.

Under the PhytoMetaSyn project, scientists at NRC and universities across Canada are investigating the metabolic pathways in approximately 75 different plant species. The ultimate goal is to engineer yeast cells to economically produce high-value natural plant compounds with interesting commercial or medical potential.

“I’m working on about ten species that make compounds called triterpenoids, which have a range of interesting properties including anti-cancer, anti-viral, anti-malarial and anti-insect potential,” says Dr. Covello.

NRC researchers in Saskatoon had similar aims. Working independently, in 2006 both the NRC and UC Berkeley teams isolated the same gene that’s involved in a key step in artemisinic acid production.

“We went on to identify other genes in the artemisinin pathway,” says Dr. Patrick Covello, who led this effort at the NRC Plant Biotechnology Institute (NRC-PBI). “Amyris and UC Berkeley together had a proven ability to make plant compounds efficiently in yeast. So we had the genes they needed and Amyris had the technology to use them in microbes.”

NRC researchers Darwin Reed (left) and Dr. Pat Covello (right) discuss mass spectrometry results used to help identify Artemisia genes.

NRC researchers Darwin Reed (left) and Dr. Pat Covello (right) discuss mass spectrometry results used to help identify Artemisia genes.

In 2008, Dr. Covello began collaborating with Dr. Chris Paddon, who was leading the effort at Amyris. Dr. Paddon and his team incorporated two key genes discovered by NRC into Amyris’ yeast system, effectively doubling the yield of the end-product and reaching the commercial targets.

Two years later, OneWorld Health announced an additional grant of $10.7 million from the Bill & Melinda Gates Foundation to scale-up the production of artemisinin, which is being handled by the global pharmaceutical firm sanofi-aventis.

In March 2011, NRC signed a license agreement with OneWorld Health and sanofi-aventis for the scale-up and production of artemisinin-based drugs through the “synthetic biology” approach developed by Amyris, UC Berkeley and NRC. The products are expected to be ready for distribution sometime in 2012.

“I’m working on about ten species that make compounds called triterpenoids, which have a range of interesting properties including anti-cancer, anti-viral, anti-malarial and anti-insect potential,” says Dr. Covello.

“When we started work on this project, nearly six years ago, we knew that it would be a tremendous challenge and opportunity from both scientific and humanitarian perspectives,” says Dr. Richard Chin, MD and CEO for OneWorld Health. “We are very pleased that the project has made great progress and that we are now ready to begin the commercialization phase in collaboration with Sanofi. The toll that malaria takes on the poorest patients in developing countries is unacceptable. Providing a stable and affordable source of artemisinin for use in artemisinin combination therapies is a breakthrough in the fight against malaria.”

About malaria

Malaria is a life-threatening parasitic disease transmitted by infected mosquitoes. 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.

Around the world, malaria causes approximately 250 million illnesses and more than one million deaths per year, of which 90 percent occur in Sub-Saharan Africa.

In many countries, malaria is the leading killer of children under five years of age. Pregnant women and their unborn children are also particularly vulnerable. In sub-Saharan Africa, up to 40 percent of low birth weight cases are due to maternal malaria, resulting in up to 400,000 infant deaths per year.

The malaria parasite is increasingly resistant to older drugs such as chloroquine. The World Health Organization recommends treating malaria using a combination of artemisinin — and other anti-malarial drugs to prolong each drug’s effectiveness and delay resistance. Artemisinin is produced by a traditional Chinese medicinal plant, called Artemisia annua, grown in Africa and Asia. But the yield from Artemisia plants is low, making artemisinin relatively expensive to produce and dependent on growing seasons, leading to unstable supplies for vulnerable groups.

Related information

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