Scientists have found new evidence that resistance to the front-line treatments for malaria is increasing.
They have confirmed that resistant strains of the malaria parasite on the border between Thailand and Burma, 500 miles (800km) away from previous sites.
Researchers say that the rise of resistance means the effort to eliminate malaria is "seriously compromised".
The details have been published in The Lancet medical journal.
In plastic and glass containers thousands of mosquitoes are hatching in a British “mosquito factory.” On strips of brown paper there are hundreds of thousands of little black mosquito eggs.
“Here we practice birth control for mosquitoes,” says Hadyn Parry, CEO of Oxitec, a British bio-research company that makes genetically modified mosquito eggs. The eggs produce sterile male mosquitoes, incapable of fertilizing the females. [Read more…]
Simulations Plus, Inc., a provider of consulting services and software for pharmaceutical discovery and development, today announced that preliminary testing shows that one of the molecules it has designed to inhibit the malaria parasite has been shown to be a potent inhibitor of the malaria parasite.
Dr. Robert Clark, director of life sciences for Simulations Plus, said: “We’re excited to announce that, as a result of initial testing of five of the compounds we designed to inhibit the Plasmodium falciparum malaria parasite, four of the five showed some inhibition of the parasite, and one of those four showed very potent inhibition at a level suitable to be a therapeutic agent. Of course, inhibiting the parasite does not necessarily mean that this molecule would be a good drug. There are many more properties that must be acceptable and years of development needed before that could happen. But this is a remarkable achievement nonetheless, because it demonstrates that using only predictions and design methods from our MedChem Studio(TM), MedChem Designer(TM), ADMET Predictor(TM), and GastroPlus(TM) software and some public domain data, we were able to design completely new chemical structures that can hit a target. There remain a few more molecules in synthesis, and those will be tested once synthesis and purification have been completed by our synthesis company, Kalexsyn, Inc., of Kalamazoo, MI. Among those molecules are the ones we believed would be the most potent inhibitors of the malaria parasite. They are a bit more difficult to synthesize, but Kalexsyn indicates that they are well along in the process and expect to complete the final steps very soon.”
Dr. Michael Lawless, team leader for cheminformatics studies for Simulations Plus, added: “The first round of tests was against the drug-sensitive strain of the malaria parasite known as 3D7. The next round will be against the drug-resistant strain — a more important measure of the potential usefulness of these new molecular structures. We hope to have results by the end of the month from those experiments. We’re shipping samples of the first five molecules to a company that will perform a series of experiments to measure a few other properties, including some physicochemical and metabolism properties. Those experiments will tell us if our predictions for some important ADME (Absorption, Distribution, Metabolism, and Excretion) properties were on the mark.”
Source: Business Wire
Bed nets and insecticides form the cornerstone of malaria prevention, with antimalarial drugs being used mainly to treat people who become ill with the disease. The drugs do have some protective effect, but it quickly wanes. Now a study in Uganda suggests that an antiretroviral drug given to HIV-infected children can boost the preventive power of a key malaria drug. [Read more…]
Researchers say a drug commonly used to treat malaria and rheumatoid arthritis has also proved effective in treating some aggressive cancers. When scientists administered hydroxychloroquine, an anti-malarial drug, together with known cancer drugs, they found it stopped the growth of cancerous tumors in two-thirds of the patients.
Scientists know that human cancer cells grow by getting energy from adjacent tumors, where cells have begun to self-destruct.
The spread of cancer is accelerated by the death of these cells.
“This process called autophagy, which literally means to self-eat, is present in all cells,” said Dr. Ravi Amaravadi. “But what we are finding in our research is that cancer cells have a very high level of autophagy even before any treatment, and so they are poised to take on the damage from existing cancer therapies and simply break down the damaged parts to fuel further growth.”
Dr. Ravi Amaravadi spoke to us via Skype. He is a cancer specialist at the University of Pennsylvania School of Medicine. His group treated patients by combining conventional cancer medications with the anti-malarial drug, hydroxychloroquine. The compound is known to inhibit autophagy and researchers hoped it could stop cancer cells from growing.
In clinical trials, scientists found that hydroxychloroquine paired poorly with some cancer drugs. But it worked well with others, such as Temsirolimus, in helping to halt tumor growth – a so-called “stable disease” rate – in patients with melanoma, an aggressive skin cancer.
“And when Temsirolimus [a cancer drug] was tested in melanoma, it had zero percent stable disease rate,” said Amaravadi. “And when we combined with hydroxychloroquine malaria drug, the stable disease rate went up to 76 percent so that’s a very big difference.”
Researchers used a high dose of hydroxychloroquine to block autophagy, much higher than what’s normally used to treat rheumatoid arthritis or malaria. The dosage has not yet proved harmful.
Dr. Davide Ruggero at the University of California, San Francisco, is also studying the growth of cancer cells. He says the results of the research with hydroxychloriquine are promising.
“This is a great discovery because we know that the compounds are not toxic – have already been used,” said Ruggero.
But Dr. Amaravadi warns that oncologists should not use the anti-malaria drug outside of clinical settings. He says hydroxychloroquine has severe side effects when combined with some cancer drugs. So the knowledge of which compounds work well together is critical.
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Source: VOA News
Dr Matthew Todd. Photo courtesy of University of Sydney.
In open source drug discovery all data and ideas are freely and immediately shared, and anyone may participate at any level.
Dr Mat Todd, from the University of Sydney’s School of Chemistry, recently led a meeting titled Open Source Drug Discovery for Malaria, to discuss the application of the open source model to discovering drugs to treat malaria.
“The open nature of the work means there are no patents and that any technology is both academically and commercially exploitable by whoever wishes to do so,” said Dr Todd.
Drug research on malaria using scientists around the world who share data in real time, unencumbered by patents, is Dr Todd’s ambition.
While no drug has so far been discovered using open source, Dr Todd led a project that used the open source approach to create a new way to produce medicine now used worldwide for the treatment of Bilharzia, a terrible parasitic disease that afflicts millions of the world’s poorest people.
His innovation won Dr Todd the Emerging Research category of the NSW Science and Engineering Awards in 2011.
Research and development of new drugs is normally done in a closed way by pharmaceutical companies, who fund the research in order to own the resultant medicines.
“This makes business sense, as there are huge profits to be made from new pharmaceuticals,” said Dr Todd.
“However, there are a number of diseases that simply do not interest pharmaceutical companies, because there’s little money to be made from these drugs. These diseases are normally ones affecting developing nations, such as malaria,” explained Dr Todd.
Taking his open source approach to finding a new drug for malaria, Dr Todd predicts that it will have the greatest benefits in the early phases – from the discovery of biologically active compounds, to improving these compounds through chemical synthesis and biological evaluation.
“Drug discovery is a complex process involving many different stages and the open source method has huge potential for improving the early phases before clinical trials have commenced.”
“I can also see the open source approach being really effective in the process chemistry phase, where we create an efficient chemical synthesis of the new drug on a large scale,” explained Dr Todd.
“I see the discussion as part of a wider series of discussions about how we’re doing science, and research more generally, in a very different way… not just about the malaria problem itself and how to tackle it, but also some of the problems that come up as we move to new science methods, and open innovation and open science,” said Professor Mary O’Kane, Chief Scientist and Engineer of NSW, who opened the meeting.
Source: University of Sydney
As researchers work to eliminate malaria worldwide, new strategies are needed to find and treat individuals who have malaria, but show no signs of the disease. The prevalence of asymptomatic or minimally symptomatic malaria can be as high as 35 percent in populations with malaria and these asymptomatic individuals can serve as a reservoir for spreading malaria even in areas where disease transmission has declined.
In a new study, researchers at the Johns Hopkins Malaria Research Institute found that a strategy of actively identifying undiagnosed malaria and then treating those with the disease resulted in significantly lower prevalence of malaria cases compared to a control group. Their findings are published in the February 3, 2012 edition of the journal PLoS ONE.
“New strategies are needed, particularly in areas of declining transmission. One strategy is to screen people for malaria and treat those who are infected, even those who are not sick enough to go to the clinic,” said lead author, Catherine G. Sutcliffe, PhD, an assistant scientist with the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology. “Using artemisinin combination therapy can enhance this strategy, as treatment can reduce transmission to mosquitoes. In regions of declining transmission, the burden of malaria could be reduced to such an extent that elimination is achievable.”
The study was conducted in southern Zambia, with colleagues from the Johns Hopkins Malaria Research Institute in Macha. Researchers analyzed data from surveys conducted in 2007 and between 2008 and 2009. In both surveys, households were screened for malaria using rapid diagnostic tests and treated with artemisinin combination therapy when malaria was detected.
According to the new study, a proactive test-and-treat case-detection strategy resulted in a sixfold reduction in prevalence in 2008 and 2009, with the initial parasite prevalence at 4 percent. Test and treat showed a twofold reduction in 2007, when community prevalence was higher at 24 percent.
“Proactive case detection with treatment using artemisinin-combination therapy can reduce transmission and provide indirect protection to household members. If resources permit, this strategy could be targeted to hot spots to achieve further reductions in malaria transmission,” said William J. Moss, MD, senior author of the study and associate professor with the Johns Hopkins Bloomberg School of Public Health.
Worldwide, malaria afflicts more than 225 million people. The disease kills between 800,000 and 1 million people each year, many of whom are children living in Africa.
Authors of “Reduced Risk of Malaria Parastemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study” include Catherine G. Sutcliffe, PhD; Tamaki Kobayashi, PhD; Harry Hamapumbu; Timothy Shields, MA; Sungano Mharakurwa, PhD; Philip E. Thuma, MD; Thomas A. Louis, PhD; Gregory Glass, PhD; and William J. Moss, MD.
The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.
The research was funded by the Johns Hopkins Malaria Research Institute.
Source: Johns Hopkins Bloomberg School of Public Health
Source: IHME
Prof. Dr. Peter H. Seeberger and Dr. François Lévesque. Copyright © MPI of Colloids and Interfaces
In future it should be possible to produce the best anti-malaria drug, artemisinin, more economically and in sufficient volumes for all patients.
The most effective anti-malaria drug can now be produced inexpensively and in large quantities. This means that it will be possible to provide medication for the 225 million malaria patients in developing countries at an affordable price.
Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam and the Freie Universität Berlin have developed a very simple process using oxygen and light for the synthesis of artemisinin, the active ingredient that pharmaceutical companies could only obtain from plants up to now. The chemists use a waste product from current artemisinin production as their starting substance. This substance can also be produced biotechnologically in yeast, which the scientists convert into the active ingredient using a simple yet very ingenious method.
There is an effective treatment against malaria, but it is not accessible to all of the more than 200 million people worldwide who are affected by the disease. Millions, especially in the developing world, cannot afford the combination drug preparation, which consists mainly of artemisinin. Moreover, the price for the medication varies, as this substance is isolated from sweet wormwood (Artemisia annua) which grows mainly in China and Vietnam, and varies seasonally in its availability.
To make the drug affordable for at least some patients in developing countries, the Clinton Foundation, for example, subsidises its cost to the tune of several million dollars per year. Nevertheless, over one million people die of malaria each year because they do not have access to effective drugs.
This may be about to change. Peter H. Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin and his colleague François Lévesque have discovered a very simple way of synthesising the artemisinin molecule, which is known as an anti-malaria drug from traditional Chinese medicine and has an extremely complex chemical structure. “The production of the drug is therefore no longer dependent on obtaining the active ingredient from plants,” says Peter Seeberger.
As a starting point, the chemists use artemisinic acid – a substance produced as a hitherto unused by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes ten times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a much simpler structure.
“We convert the artemisinic acid into artemisinin in a single step,” says Peter Seeberger. “And we have developed a simple apparatus for this process, which enables the production of large volumes of the substance under very controlled conditions.” The only reaction sequence known up to now required several steps, following each of which the intermediate products had to be isolated laboriously—a method that was far too expensive to offer as a viable alternative to the production of the drug from plants.
The striking simplification of artemisinin synthesis required not only a keen sense for an elegant combination of the correct partial reactions to enable the process to take place in a single step; it also took a degree of courage, as the chemists departed from the paths typically taken by industry up to now. The effect of the molecule, which not only targets malaria but possibly also other infections and even breast cancer, is due to, among other things, a very reactive chemical group formed by two neighbouring oxygen atoms, which chemists refer to as an endoperoxide.
Peter Seeberger and François Lévesque use photochemistry to incorporate this structural element into the artemisinic acid. Ultraviolet light converts oxygen into a form that can react with molecules to form peroxides.
“Photochemistry is a simple and cost-effective method. However, the pharmaceutical industry has not used it to date because it was so difficult to control and implement on a large scale,” explains Peter Seeberger. In the large reaction vessels with which industrial manufacturers work, flashes of light do not penetrate deeply enough from outside and the reactive form of oxygen is not produced in sufficient volumes.
The Potsdam-based scientists have succeeded in resolving this problem using an ingenious trick: They channel the reaction mixture containing all of the required ingredients through a thin tube that they have wrapped around a UV lamp. In this structure, the light penetrates the entire reaction medium and triggers the chemical conversion process with optimum efficiency.
“The fact that we do not carry out the synthesis as a one-pot reaction in a single vessel, but in a continuous-flow reactor enables us to define the reaction conditions down to the last detail,” explains Peter Seeberger. After just four and a half minutes a solution flows out of the tube, in which 40 percent of the artemisinic acid has become artemisinin. “We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin,” says Peter Seeberger.
And it could all happen very quickly. Peter Seeberger estimates that the innovative synthesis process could be ready for technical use in a matter of six months. This would alleviate the global shortage of artemisinin and exert considerable downward pressure on the price of the associated drugs.
Reference: François Lévesque and Peter H. Seeberger
“Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin”
Angewandte Chemie international edition, 17. January 2012; DOI: 10.1002/anie.201107446
Source: Max Planck Institute of Colloids and Interfaces
Hopes of at last controlling malaria in Africa could be dashed by the emergence of poor-quality and fraudulent antimalarial medicines, warn experts writing in Malaria Journal. Unless urgent action is taken both within Africa and internationally, they argue, millions of lives could be put at risk. [Read more…]