U.S. Investments to Battle Malaria Show Results

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Progress against Malaria is one area where U.S. investments in global health have made an great impact. Just five years ago, it was estimated that malaria killed nearly one million children annually in sub-Saharan Africa. The economic cost to the continent was estimated to be nearly $30 billion each year in lost productivity.

“Today, the U.S. along with its partners have helped cut malaria cases in half in more than 40 countries and reduced childhood malarial deaths by 200,000, and even seen a reduction in all-cause child mortality in seven initial Presidential Malaria Initiative countries,” said USAID Administrator Raj Shah. He added, “I find that statistic astounding.”

The President’s Malaria Initiative, which is led by the U.S. Agency for International Development and implemented jointly with the Centers for Disease Control and Prevention, has led the fight against this preventable and curable disease which is currently the leading cause of death among children in Africa.

“Today, we have a lot to celebrate, because the rates of death resulting from malaria infection are decreasing,” said Rear Admiral Tim Ziemer, the U.S. Global Malaria Coordinator. “However, we need to be sobered by the job ahead of us.”

That’s because despite lower infection and death rates, and despite the fact that the disease is both preventable and treatable, it is estimated that a child in Africa still dies every 45 seconds from malaria.

The President’s Malaria Initiative, now a central part of the Global Health Initiative, was introduced in 2005 to concentrate on fighting the disease.  Its goal is to reduce malaria-related deaths by 50 percent in 15 focus countries by the year 2016.

[“We] believe we can push the Initiative’s success even further,” said USAID Administrator Raj Shah.  “Over the next five years, . . . .we can save an additional 500,000 lives a year, most of them young children.”

To do so, the U.S will work with partners to train health care workers to quickly identify whether a fever is caused by malaria; develop more effective insecticides that kill the mosquitoes without harming people; and we must find cheaper, more efficient ways to produce artemisinin.

“Finally,” said Dr. Shah, “we need to seek the ultimate answer to malaria: a cheap, effective vaccine. Through the Malaria Vaccine Initiative, USAID will support the development and testing of promising candidates.”

Source: VOA News

The Institute for OneWorld Health Announces Development of Alternative Source of Artemisinin

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The Institute for OneWorld Health (iOWH), a non-profit drug development organization, announced today that its development of an alternative source of artemisinin using pioneering synthetic biology technology (semisynthetic artemisinin (ART) project) has successfully entered the production and distribution phase.

The semisynthetic version of artemisinin is targeted to be an affordable, non-seasonal and complementary source of ART and will stabilize price volatility and alleviate shortages – key factors in meeting future demand in developing nations and around the globe.

iOWH, in collaboration with its strategic partners, successfully completed the scientific work necessary to enter the production and distribution phase of the project. Through a unique public-private partnership with sanofi-aventis, a leading global pharmaceutical company, this phase will enable production of semisynthetic ART. Sanofi has made essential contributions during the project’s development and industrialization phase, and is going to manufacture and distribute the semi synthetic artemisinin version to any qualified buyer. The substantial investment sanofi-aventis is making in this project will make it possible to facilitate integration of semisynthetic ART into the ACTs and the global supply chain, with an estimated goal to begin distribution in 2012.

“When we started work on this project, nearly six years ago, we knew that this would be a major challenge from technical, scientific, and humanitarian standpoints. Here we are today; however, ready to begin the production and distribution phase in collaboration with sanofi, thanks to the hard work of our team, our collaborators, and our subgrantees, as well as generous support from our funders. Our goal is that one day; no child will die from malaria. Providing an alternative source of artemisinin is a breakthrough in the fight against malaria,” said Richard Chin, M.D., CEO of iOWH.

“Realizing this project brings us enormous satisfaction that only our profession, devoted to public health and patient care, can offer. Contributing to a project which saves lives and relieves suffering within the context of a fair trade economic model, combined with technological challenges and partnership, is a source of inspiration for all members of our team,” said Francis Carré, CEO of Sanofi Chimie.

iOWH has led this project, funded by the Bill & Melinda Gates Foundation, in collaboration with Amyris Inc. and sanofi-aventis. The synthetic biology technology is based on pioneering inventions licensed from the University of California at Berkeley and the University of Saskatchewan. Headquartered in South San Francisco, iOWH is a non-profit that discovers, develops and delivers safe, effective and affordable new medicines for vulnerable population with infectious diseases in the developing world, with emphasis on diseases that disproportionately affect children.

Source: Business Wire

Canadian Researchers Develop Inexpensive Malaria Treatment

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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

Seaweed May Hold Secrets to Fighting Malaria

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Julia Kubanek, an associate professor at the Georgia Institute of Technology, holds samples of a tropical seaweed whose surface chemicals are being studied for their potential antimalarial properties. Photo by Gary Meek, Courtesy Georgia Tech.

A group of chemical compounds used by a species of tropical seaweed to ward off fungus attacks may have promising antimalarial properties for humans. The compounds are part of a unique chemical signaling system that seaweeds use to battle enemies – and that may provide a wealth of potential new pharmaceutical compounds.

Using a novel analytical process, researchers at the Georgia Institute of Technology found that the complex antifungal molecules are not distributed evenly across the seaweed surfaces, but instead appear to be concentrated at specific locations – possibly where an injury increases the risk of fungal infection.

A Georgia Tech scientist will report on the class of compounds, known as bromophycolides, at the annual meeting of the American Association for the Advancement of Science (AAAS) Feb. 21, 2011 in Washington, D.C. The research, supported by the National Institutes of Health, is part of a long-term study of chemical signaling among organisms that are part of coral reef communities.

“The language of chemistry in the natural world has been around for billions of years, and it is crucial for the survival of these species,” said Julia Kubanek, an associate professor in Georgia Tech’s School of Biology and School of Chemistry and Biochemistry. “We can co-opt these chemical processes for human benefit in the form of new treatments for diseases that affect us.”

More than a million people die each year from malaria, which is caused by the parasite Plasmodium falciparum. The parasite has developed resistance to many antimalarial drugs and has begun to show resistance to artemisinin – today’s most important antimalarial drug. The stakes are high because half of the world’s population is at risk for the disease.

“These molecules are promising leads for the treatment of malaria, and they operate through an interesting mechanism that we are studying,” Kubanek explained. “There are only a couple of drugs left that are effective against malaria in all areas of the world, so we are hopeful that these molecules will continue to show promise as we develop them further as pharmaceutical leads.”

In laboratory studies led by Georgia Tech student Paige Stout from Kubanek’s lab – and in collaboration with California scientists – the lead molecule has shown promising activity against malaria, and the next step will be to test it in a mouse model of the disease. As with other potential drug compounds, however, the likelihood that this molecule will have just the right chemistry to be useful in humans is relatively small.

Other Georgia Tech researchers have begun research on synthesizing the compound in the laboratory. Beyond producing quantities sufficient for testing, laboratory synthesis may be able to modify the compound to improve its activity – or to lessen any side effects. Ultimately, yeast or another microorganism may be able to be modified genetically to grow large amounts of bromophycolide.

The researchers found the antifungal compounds associated with light-colored patches on the surface of the Callophycus serratus seaweed using a new analytical technique known as desorption electrospray ionization mass spectrometry (DESI-MS). The technique was developed in the laboratory of Facundo Fernandez, an associate professor in Georgia Tech’s School of Chemistry and Biochemistry. DESI-MS allowed researchers for the first time to study the unique chemical activity taking place on the surfaces of the seaweeds.

As part of the project, Georgia Tech scientists have been cataloging and analyzing natural compounds from more than 800 species found in the waters surrounding the Fiji Islands. They were interested in Callophycus serratus because it seemed particularly adept at fighting off microbial infections.

Using the DESI-MS technique, researchers Leonard Nyadong and Asiri Galhena analyzed samples of the seaweed and found groups of potent antifungal compounds. In laboratory testing, graduate student Amy Lane found that these bromophycolide compounds effectively inhibited the growth of Lindra thalassiae, a common marine fungus.

“The alga is marshalling its defenses and displaying them in a way that blocks the entry points for microbes that might invade and cause disease,” Kubanek said. “Seaweeds don’t have immune responses like humans do. But instead, they have some chemical compounds in their tissues to protect them.”

Though all the seaweed they studied was from a single species, the researchers were surprised to find two distinct groups of antifungal chemicals. From one seaweed subpopulation, dubbed the “bushy” type for its appearance, 23 different antifungal compounds were identified. In a second group of seaweed, the researchers found 10 different antifungal compounds — all different from the ones seen in the first group.

In the DESI-MS technique, a charged stream of polar solvent is directed at the surface of a sample under study at ambient pressure and temperature. The spray desorbs molecules, which are then ionized and delivered to the mass spectrometer for analysis.

“Our collaborative team of researchers from the Department of Biomedical Engineering and the College of Sciences has worked within the Bioimaging Mass Spectrometry Center at Georgia Tech to better understand the mechanisms of chemical defenses in marine organisms,” said Fernandez. “This is an example of cross-cutting interdisciplinary research that characterizes our institute.”

Kubanek is hopeful that other useful compounds will emerge from the study of signaling compounds in the coral reef community.

“In the natural world, we have seaweed that is making these molecules and we have fungi that are trying to colonize, infect and perhaps use the seaweed as a substrate for its own growth,” Kubanek said. “The seaweed uses these molecules to try to prevent the fungus from doing this, so there is an interaction between the seaweed and the fungus. These molecules function like words in a language, communicating between the seaweed and the fungus.”

Source: Newswise

 

NITD609 Compound May Be Promising Malaria Drug Candidate, Say Researchers

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A chemical that rid mice of malaria-causing parasites after a single oral dose may eventually become a new malaria drug if further tests in animals and people uphold the promise of early findings. The compound, NITD609, was developed by an international team of researchers.

“Although significant progress has been made in controlling malaria, the disease still kills nearly 1 million people every year, mostly infants and young children,” says NIAID Director Anthony S. Fauci, M.D. “It has been more than a decade since the last new class of antimalarials—artemisinins—began to be widely used throughout the world. The rise of drug-resistant malaria parasites further underscores the need for novel malaria therapies.”

Dr. Fauci adds that the compound “appears to target a parasite protein not attacked by any existing malaria drug, and has several other desirable features. This research is also a notable example of successful collaboration between government-supported scientists and private sector researchers.”

The study, in the Sept. 3, 2010 issue of Science, was led by Thierry T. Diagana, Ph.D., of the Novartis Institute for Tropical Diseases (NITD), and Dr. Winzeler. Dr. Winzeler is affiliated with The Scripps Research Institute and the Genomic Institute of the Novartis Research Foundation, La Jolla, Calif.

Work on what eventually became NITD609 began in Dr. Winzeler’s lab in 2007. Scientists screened 12,000 chemicals using an ultra-high throughput robotic screening technique customized to detect compounds active against Plasmodium falciparum, the most deadly malaria parasite. The screen identified a chemical with good parasite-killing abilities and the potential to be modified into a drug. Medicinal chemists at the NITD then synthesized and evaluated about 200 versions of the original compound to arrive at NITD609, which could be formulated as a tablet and manufactured in large quantities. NITD609 is one of a new class of chemicals, the spiroindolones, which have been described in recently published research by Dr. Winzeler and colleagues as having potent effects against two kinds of malaria parasites.

“From the beginning, NITD609 stood out because it looked different, in terms of its structure and chemistry, from all other currently used antimalarials,” says Dr. Winzeler. “The ideal new malaria drug would not just be a modification of existing drugs, but would have entirely novel features and mechanism of action. NITD609 does.”

Source: NIH