Sweep yields leads for new malaria drugs

Researchers hope the studies’ findings will lead to a new generation of antimarial drugs (Source: WEHI/Drew Berry)

A massive screening of chemicals has turned up thousands of compounds that could lead to new drugs in the fight against malaria, according to a pair of studies published today.

Malaria affects a quarter of a billion people worldwide, and claims upward of 850,000 lives every year, particularly children in the poorer nations of Africa and Asia.

Preventative measures such as the use of insecticide-treated bed nets has helped cut infection rates dramatically in some of the worst-hit countries, and treatments based on a class of drugs called artemisinin have sharply reduced mortality.

But the rise of new, drug-resistant strains of the disease could wipe out that progress unless alternative compounds are found, the World Health Organization (WHO) has warned.

Multiple targets

An international team of researchers led by R Kiplin Guy of St Jude Children’s Research Hospital in Memphis, Tennessee combed through more than 300,000 candidate chemicals.

Their study, published in the journal Nature, identified 1100 agents out of more than 300,000 candidates that inhibited growth of the deadly Plasmodium falciparum parasite that causes the disease by at least 80%.

A more select subset of 172 compounds all had chemical structures unlike those in existing anti-malarial drugs, according to the study.

The fact that these novel agents acted on different targets in the mosquito-borne parasite could prove crucial in beating back the emerging threat of drug-resistant variants.

As a proof of principle, the researchers showed that one of the compounds was effective in treating malaria in a mouse model, albeit at a very high concentration.

Going public

In a second study, also appearing in Nature, Jose Garcia-Bustos of GlaxoSmithKline and colleagues screened around two million agents in the pharmaceutical giant’s in-house chemical library.

Setting a similar threshold for blocking the parasite’s growth, the researchers uncovered 13,500 promising active compounds.

Significantly, 8000 of them were equally effective against multi-drug resistant P. falciparum parasites.

More than 11,000 of the “hits” were proprietary compounds owned by the drug company, which has taken the unusual step of transferring them to the public domain, where they are available researchers anywhere in the world.

“These reports offer tremendous opportunities to develop the next generation of antimalarial drugs,” says David Fidock, a researcher at the Columbia University Medical Center in New York.

Also writing in Nature, Fidock cautions that it is only a “starting point,” and that time was running short.

Reference Link
http://www.abc.net.au/science/articles/2010/05/20/2904634.htm?site=science&topic=latest

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ABC

Frog gene map a leap forward for humans

Scientists have for the first time sequenced the genome of a frog and in the process made an interesting discovery; some of its genetic makeup is similar to humans.

The international team of scientists, led by Uffe Hellsten of the Joint Genome Institute in the United States, has published the first genome analysis of the frog Xenopus tropicalis today in the journal Science.

Professor Grant Morahan, a geneticist at the University of Western Australia says the findings are significant.

“[You’ve] probably heard of the human genome program and the mouse genome program, but this is the first organism that has been sequenced that is an intermediate between fish and reptiles,” he says.

The researchers found nearly 80% of all human genes associated with genetic diseases are shared with the Xenopus, including more than 1700 genes that are very similar to conditions such as cancer, asthma and heart disease.

Great potential

Professor Phil Batterham of the University of Melbourne, says the similar genetic architecture means there is potential for frogs to help solve human problems.

“The specific biological advantage is that frogs develop outside the body of their mothers so you can actually watch development proceed and that is a huge advantage,” he says.

“You can manipulate these organisms and work with them and experiment on them and really find the answers to many important questions that can be related to human health.”

Frog specialist Professor Michael Tyler says the researchers chose Xenopus for its small genome size and because it is so common.

“Xenopus is a group of frogs confined to southern Africa better known as clawed frogs,” he says.

“They live in water almost entirely. They have claws on the end of their fingers and toes, so they are rather extraordinary. There is probably no country in the world that has biological laboratories where these animals are not being kept in captivity.”

Morahan says Xenopus is not as biologically relevant for human health as other species.

“I assume we will know the genome sequences of maybe 20 different mouse strains so we’ll know this in much more detail than we know the frog sequence,” he says.

Reference Link
http://www.abc.net.au/science/articles/2010/04/30/2886742.htm?site=science&topic=latest

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ABC