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New hope for advances in treating malaria
April 22, 2009Researchers at the University of Leeds have developed chemicals which kill the most deadly malaria-causing parasite, Plasmodium falciparum -- including those resistant to existing drugs.
The compounds work by preventing the enzyme dihydroorotate dehydrogenase (DHODH) - essential to the growth of the parasite - from working, which results in its death.
Says lead researcher Dr Glenn McConkey, from Leeds' Faculty of Biological Sciences: "Without this enzyme, Plasmodium falciparum is unable to grow and therefore it dies. The inhibitors developed at Leeds bind to the DHODH enzyme in the parasite and stop it functioning, preventing the proliferation of the parasites, which live in red blood cells. In addition, our chemicals are equally effective against parasites that have developed resistance to drugs."¯
He adds: "DHODH in humans is not an essential enzyme, so by concentrating our studies on it we can develop chemical inhibitors that have a negative impact on the parasite without any major side-effects to the human host. In effect we are exploiting a biological difference, and this will allow us to develop potent, selective inhibitors."¯
According to the World Health Organisation (WHO), malaria kills a million people across the globe each year, with forty per cent of the world's population at risk of contracting the disease. WHO also estimates that a child dies from malaria every 30 seconds.
Dr McConkey says: "Our chemicals are particularly exciting as they kill malaria parasites at low concentrations, something that is important for medicines as they are massively diluted on entering the bloodstream and, unlike many pharmaceutical products, we have a firm understanding of the molecular basis of their action. This project highlights the benefits of combining biological and chemistry disciplines."¯
Dr McConkey says the next stage of this research is to develop a larger collection of potent inhibitors and to see how these chemicals work alongside commonly used treatments.
"The parasites responsible for malaria have been very effective at developing resistance to existing drugs and efforts to find replacements are often stymied by the rate of resistance. Therefore it is essential that new products work effectively in combination with those already on the market,"¯ he says.
This work was supported in part by a WHO Tropical Diseases Research Grant and a grant from Medicines for Malaria Venture. The research is published in the latest edition of the Journal of Medicinal Chemistry.
University of Leeds
He adds: "DHODH in humans is not an essential enzyme, so by concentrating our studies on it we can develop chemical inhibitors that have a negative impact on the parasite without any major side-effects to the human host. In effect we are exploiting a biological difference, and this will allow us to develop potent, selective inhibitors."¯
According to the World Health Organisation (WHO), malaria kills a million people across the globe each year, with forty per cent of the world's population at risk of contracting the disease. WHO also estimates that a child dies from malaria every 30 seconds.
Dr McConkey says: "Our chemicals are particularly exciting as they kill malaria parasites at low concentrations, something that is important for medicines as they are massively diluted on entering the bloodstream and, unlike many pharmaceutical products, we have a firm understanding of the molecular basis of their action. This project highlights the benefits of combining biological and chemistry disciplines."¯
Dr McConkey says the next stage of this research is to develop a larger collection of potent inhibitors and to see how these chemicals work alongside commonly used treatments.
"The parasites responsible for malaria have been very effective at developing resistance to existing drugs and efforts to find replacements are often stymied by the rate of resistance. Therefore it is essential that new products work effectively in combination with those already on the market,"¯ he says.
This work was supported in part by a WHO Tropical Diseases Research Grant and a grant from Medicines for Malaria Venture. The research is published in the latest edition of the Journal of Medicinal Chemistry.
University of Leeds
Malaria Current Events and Malaria News RSSPATH Malaria Vaccine Initiative shares strategy for developing 'next-generation' malaria vaccines
Marking its tenth anniversary year, the PATH Malaria Vaccine Initiative (MVI) today unveiled a new strategy that sets the stage for an aggressive push targeting the long-term goal of eliminating and eradicating malaria. Malaria is one of the world's deadliest infectious diseases, killing nearly 900,000 people a year, most of them children in sub-Saharan Africa.
Global challenges and opportunities in fighting HIV/AIDS and neglected diseases
Responding to the HIV/AIDS pandemic and tackling so-called neglected tropical diseases are the focus of the November/December 2009 edition of Health Affairs.
Media availability: The role of biomedical research in malaria eradication
Although malaria has been controlled in many local and regional populations, the permanent elimination of malaria parasites throughout the world remains an elusive goal, and the disease continues to claim nearly one million lives each year.
Ineffective monotherapies common in high-burden malarious countries
ACTwatch, a research project led by PSI, in collaboration with the London School of Hygiene and Tropical Medicine, released evidence today that indicates that artemisinin combination therapy, the most effective medicines for treating malaria, continue to have a significantly low presence on the market among populations considered to be most at risk.
New tool promises more accurate antimalarial drug dosing
Scientists at LSTM have developed a tool to support the development of appropriate age-based dosing regimens for malaria drugs.
Cell phones become handheld tools for global development
Mobile phones are on the verge of becoming powerful tools to collect data on many issues, ranging from global health to the environment.
Exon-skipping drug prevents muscle wasting, maintains muscle function in dystrophin deficient mice
An exon skipping PPMO has demonstrated dramatic effects in the prevention and treatment of severely affected, dystrophin and utrophin-deficient mice, preventing severe deterioration of the treated animals and extending their lifespan.
UM School of Medicine researchers find extreme genetic variability in malaria parasite
Researchers at the University of Maryland School of Medicine Center for Vaccine Development (CVD) have charted the extreme genetic differences that occur over time in the most dangerous malaria parasite in the world.
Outfoxing pox: Developing a new class of vaccine candidates
In the annals of medicine, Edward Jenner's 1796 vaccination of a young boy against smallpox, using fluid from cowpox blisters, remains a landmark case. In a new study, Kathryn Sykes, a researcher at Arizona State University's Biodesign Institute and her colleagues have taken a fresh look at cowpox.
Ironing out the genetic cause of hemoglobin problems
A gene with a significant effect on regulating hemoglobin in the body has been identified as part of a genome-wide association study, which looked at the link between genes and hemoglobin level in 16,000 people.
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