malaria drugs Archives

April 21, 2011April 26, 2011

Genetically Modified Mosquitoes Offer Malaria Hope

By James Gallagher Health and Science reporter, BBC News

Scientists believe they are closer to being able to change the DNA of wild mosquitoes in order to combat malaria.

In the laboratory, they made a gene spread from a handful of mosquitoes to most of the population in just a few generations, according to a report in Nature.

If the right gene can be made to spread then researchers hope to reduce the number of cases of malaria.

Other academics have described the study as a “major step forward”.

The World Health Organisation estimated that malaria caused nearly one million deaths in 2008.

Spreading resistance

GM mosquito — Around a million people are thought to die from malaria each year

Research groups have already created “malaria-resistant mosquitoes” using techniques such as introducing genes to disrupt the malaria parasite’s development.

The research, however, has a great challenge – getting those genes to spread from the genetically-modified mosquitoes to the vast number of wild insects across the globe.

Unless the gene gives the mosquito an advantage, the gene will likely disappear.

Scientists at Imperial College London and the University of Washington, in Seattle, believe they have found a solution.

They inserted a gene into the mosquito DNA which is very good at looking after its own interests – a homing endonuclease called I-SceI.

The gene makes an enzyme which cuts the DNA in two. The cell’s repair machinery then uses the gene as a template when repairing the cut.

As a result the homing endonuclease gene is copied.

It does this in such a way that all the sperm produced by a male mosquito carry the gene.

So all its offspring have the gene. The process is then repeated so the offspring’s offspring have the gene and so on.

In the laboratory experiments, the gene was spread to half the caged mosquitoes in 12 generations.

Defeating malaria

Professor Andrea Crisanti, from the department of life sciences at Imperial College London, said: “This is an exciting technological development, one which I hope will pave the way for solutions to many global health problems.

“At the beginning I was really quite skeptical and thought it probably would not work, but the results are so encouraging that I’m starting to change my mind.”

He said the idea had been proved in principle and was now working on getting other genes to spread in the same way.

He believes it could be possible to introduce genes which will make the mosquito target animals rather than humans, stop the parasite from multiplying in the insect or produce all male offspring which do not transmit malaria.

Professor Janet Hemingway, from the Liverpool School of Tropical Medicine, said the work was an “exciting breakthrough”.

She cautioned that the technique was still some way off being used against wild mosquitoes and there were social issues around the acceptability of using GM technology.

“This is however a major step forward providing technology that may be used in a cost effective format to drive beneficial genes through mosquito populations from relatively small releases,” she added.

Dr Yeya Touré, from the World Health Organisation, said: “This research finding is very important for driving a foreign gene in a mosquito population. However, given that it has been demonstrated in a laboratory cage model, there is the need to conduct further studies before it could be used as a genetic control strategy

March 19, 2011

Canadians Make Malaria Breakthrough

Mother and daughter sleep under mosquito net to prevent bites from the parasite carrying mosquito

Lana Haight, Postmedia News

SASKATOON — Scientists in Saskatoon have developed an inexpensive malaria treatment that will help the million people who die every year from the infection.

“This is the most important drug in the treatment of malaria today. The World Health Organization says it should be the first line of defence,” said Patrick Covello, a senior research officer at the National Research Council in Saskatoon.

Covello and his team figured out a way to produce a difficult-to-cultivate chemical needed to build effective malaria drugs.

The breakthrough was announced Friday at the National Research Council Plant Biotechnology Institute.

The best drugs available to fight malaria are made with artemisinin, a compound derived from the sweet wormwood plant found in parts of Asia and Africa. But cultivating and harvesting the plant and then extracting artemisinin is time-consuming and labour intensive, says Covello. And the supply of the natural compound is also dependent on weather and growing conditions.

In 2003, Covello began work to identify the genes in the wormwood plant that produce the protein that leads to artemisinin.

“We identified four genes in what we call the pathway to artemisinin in the plant,” he said in an interview.

Meanwhile, University of California at Berkley researchers found they could develop a precusor to artemisinin by introducing chemicals into yeast.

Covello contacted Amyris Technologies, a spinoff company from the Berkeley research group, to suggest it use the genes his group had identified in the wormwood plant. When two of the genes identified in Saskatoon were introduced to the yeast compound developed at Berkeley, the production of artemisinin doubled.

The Institute for OneWorld Health, the American-based organization that has led the project to develop the semi-synthetic artemisinin, and pharmaceutical company Sanofi-aventis jointly announced on Friday that the drug company is preparing to ramp up production using the genes identified in Saskatoon.

The Bill & Melinda Gates Foundation, which has already contributed $42.6 million toward the American research, is also supporting the production of the drug to ensure it will be available on a not-for-profit basis for the developing world.

“The idea is to provide the developing world with antimalarial drugs at the lowest possible cost and, in addition, to provide a very stable supply because this yeast-fermentation process is shorter term and more reliable than growing the plants themselves,” said Covello.

Covello understands that Sanofi-aventis will begin commercial-scale production in 2012.

The federal government has spent $869,000 over eight years to support the Saskatoon research.

“Our government is committed to improving the health of women and children in developing countries,” said Gary Goodyear, minister of state for science and technology, in a government news release.

“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.”

The Vancouver Sun

February 11, 2011February 14, 2011

Do Not Tax Anti-Malaria Medicines and Products

Malaria advocacy group, Malaria Taxes and Tariffs Advocacy Project (M-TAP), is insisting that governments drop all taxes and tariffs on medicines, mosquito nets and other anti-malaria tools in order to bring down the costs of the products and facilitate their delivery to the people who need it.

M-TAP says only six countries worldwide have completely removed tariffs on products used to fight the disease, despite a promise 10 years ago from African leaders to do so.

Campaigners say dropping taxes and tariffs can play a key role in cutting costs because the vast majority of drugs and other products used to fight malaria are imported from overseas.

To date, M-TAP says, only the African countries of Guinea, Kenya, Mauritius, Tanzania and Uganda and the Asian nation of Papua New Guinea have done away with tariffs on commodities recommended by the World Health Organization (WHO) as essential to effective malaria control.

These include long-lasting insecticide-treated bednets, malaria drugs known as artemisinin-based combination therapies (ACTs), rapid diagnostic tests, insecticides for indoor spraying, and insecticide spray pumps.

M-TAP, which has been gathering evidence from nearly 80 malaria-hit countries over the past two years, said it found that taxes and tariffs on anti-malaria products provide only minimal revenues, and these gains are often offset by health costs and lost productivity from preventable malaria illnesses.

Taxes and tariffs may also prevent the poor from gaining access to malaria treatment, the group said.

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January 19, 2011January 20, 2011

Caught in The Act: Imaging Microscopy Catches Malaria Parasite Invading Blood Cells

Australian scientists using new image and cell technologies have for the first time caught malaria parasites in the act of invading red blood cells. The researchers, from the Walter and Eliza Hall Institute in Melbourne, Australia, and the University of Technology, Sydney (UTS), achieved this long-held aim using a combination of electron, light and super resolution microscopy, a technology platform new to Australia.

The detailed look at what occurs as the parasite burrows through the walls of red blood cells provides new insights into the molecular and cellular events that drive cell invasion and may pave the way for developing new treatments for malaria. Institute researchers Dr Jake Baum, Mr David Riglar, Dr Dave Richard and colleagues from the institute’s Infection and Immunity division led the research with colleagues from the i3 institute at UTS.

Dr Baum said the real breakthrough for the research team had been the ability to capture high-resolution images of the parasite at each and every stage of invasion, and to do so reliably and repeatedly. Their findings are published in today’s issue of the journal Cell Host & Microbe.

“It is the first time we’ve been able to actually visualise this process in all its molecular glory, combining new advances developed at the institute for isolating viable parasites with innovative imaging technologies,” Dr Baum said.

“Super resolution microscopy has opened up a new realm of understanding into how malaria parasites actually invade the human red blood cell. Whilst we have observed this miniature parasite drive its way into the cell before, the beauty of the new imaging technology is that it provides a quantum leap in the amount of detail we can see, revealing key molecular and cellular events required for each stage of the invasion process.”

The imaging technology, called OMX 3D SIM super resolution microscopy, is a powerful new 3D tool that captures cellular processes unfolding at nanometer scales. The team worked closely with Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull from the i3 institute at UTS to capture these images.

“This is just the beginning of an exciting new era of discoveries enabled by this technology that will lead to a better understanding of how microbes such as malaria, bacteria and viruses cause infectious disease,” Associate Professor Whitchurch said.

Dr Baum said the methodology would be integral to the development of new malaria drugs and vaccines. “If, for example, you wanted to test a particular drug or vaccine, or investigate how a particular human antibody works to protect you from malaria, this imaging approach now gives us a window to see the actual effects that each reagent or antibody has on the precise steps of invasion,” he said.

Malaria is caused by the Plasmodium parasite, which is transmitted by the bite of infected mosquitoes. Each year more than 400 million people contract malaria, and as many as a million, mostly children, die.

“Historically it has been very difficult to both isolate live and viable parasites for infection of red blood cells and to employ imaging technologies sensitive enough to capture snapshots of the invasion process with these parasites, which are only one micron (one millionth of a metre) in diameter,” Dr Baum said.

He said one of the most interesting discoveries the imaging approach revealed was that once the parasite has attached to the red blood cell and formed a tight bond with the cell, a master switch for invasion is initiated and invasion will continue unabated without any further checkpoints.

“The parasite actually inserts its own window into the cell, which it then opens and uses to walk into the cell, which is quite extraordinary,” Dr Baum said. “Visually tracking the invasion of Plasmodium falciparum into a red blood cell is something I’ve been aiming at ever since I began at the Walter and Eliza Hall Institute in 2003; it’s really thrilling to have reached that goal. This technology enables us to look at individual proteins that we always knew were involved in invasion, but we never knew what they did or where they were, and that, we believe, is a real leap for malaria researchers worldwide

This work was supported by the National Health and Medical Research Council, The University of Melbourne, Canadian Institutes of Health, the University of Technology, Sydney, and the Australian Research Council.

This image is a composite showing the behavior of different parts of the malaria parasite as it invades a red blood cell, at nanometer scales. The three components of the malaria parasite are labeled with fluorescent proteins (blue = parasite nucleus, red = secretory organelle, green = tight junction). The red blood cell is superimposed on the image for context. Image 1 (Attachment): The parasite is about to invade the red blood cell (unseen to the right of the picture). The tight junction (green) is like a window that the parasite brings with it and inserts into the red blood cell to gain entry. Image 2 (Invasion): This image is mid-invasion, the first time this step has even been visualized. The parasite "opens" the window it has inserted into the cell, and walks through. The secretory organelle (red) secretes its contents through the tight junction (green) and creates a vacuole which the parasite lives within in the red blood cell. In this image we see the parasite nucleus (blue) moving through the ‘window’ into the cell. Image 3 (Sealing): The parasite has completed invasion and is within a vacuole inside the host red blood cell. The window has been closed again, and will break down at a later stage. The parasite is now enclosed within its vacuole (red), the nucleus (blue) showing the parasite safely inside.

Penny Fannin

fannin@wehi.edu.au