Discovery Provides New Drug Targets For Malaria Cure

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11th January 2010, 12:31pm - Views: 446





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Discovery provides new drug targets for malaria cure


Strictly embargoed until 7am Australian EST Tuesday 12 January 2010/ 

3pm Monday US EST Monday 11 January 2010.


Researchers are a step closer to developing new antimalarial drugs after discovering the normal function

of a set of proteins related to the malaria parasite protein, which causes resistance to the front-line drug

chloroquine. The findings also provide a novel tool for studying the malarial chloroquine-resistance factor.


The study examined transporter proteins which are known to move compounds around the cell. The genes

for these proteins are present in plants as well as the malaria parasite Plasmodium falciparum (known as

clt and PfCRT respectively), so researchers used the model plant Arabidopsis to reveal that these proteins

normally transport glutathione, an antioxidant which protects the cell from stresses.


In the malaria parasite (a single cell organism), this type of transporter protein has mutated so that it no

longer functions normally, enabling it to remove the drug chloroquine from its cell and survive.


Plasmodium falciparum is the most dangerous of the malaria infections being transmitted by the female

Anopheles mosquito. It has the highest rates of complications and mortality and is responsible for up to

one million deaths per year, mostly children in Africa under the age of five. The evolution of drug-resistant

Plasmodium strains, especially those resistant to chloroquine, has had major impacts on global public

health. The economic toll is also huge with malaria infection destroying more than 1% of African GPD.


The work was led by Dr Spencer Maughan who began researching these genes in Prof. Chris Cobbett’s

lab in the Department of Genetics at the University of Melbourne and involved an international team from

the Universities of Melbourne, Cambridge (UK), Heidelberg (Germany), Liverpool (UK) and Rothamsted

Research (UK). It will be published in the prestigious international journal PNAS this week.


“Our findings set in motion the chance of reclaiming the efficacy of chloroquine which could turn the tide on

the war against malaria and ultimately may help save millions of lives,” said Dr Maughan.


“The transporter is normally essential to the survival of the malaria parasite and when mutated, provides

the extra advantage of removing the drug chloroquine from its cell.


“We hope that understanding the normal role of the transporter in plants will be a key step in malaria

research. Unlike in the plant, if the gene for the transporter is inactivated in malaria, the parasite dies,

preventing more study into its role. The plant could therefore provide a useful tool in malaria research.”


“These results describe the first missing link in understanding this class of proteins and could provide a

two-pronged treatment approach- preventing malaria removing chloroquine from its cell and enabling the

design of new drugs based on the shape of glutathione.”


For more information: Dr Spencer Maughan, +1 650 521 7203, Email: smaughan@venrock.com; Dr Nerissa Hannink, Media

Officer, University of Melbourne, Ph. 0430 588 055. Note: Dr Maughan is in the US and will be available for interview on Monday

11 and Tuesday 12 January AEST, from 9 am to 5pm only (corresponding to Sunday 10 and Monday 11 January, 2 to 10pm US

West coast time).

Media Release

Strictly embargoed until 12 January AEST

Attention: Newsdesk

Issued: Monday 11 January 2010






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