Study reveals secret of severe malaria's sticky proteins

A study by Swedish and Ugandan scientists has shed new light on how ‘sticky’ proteins produced by the malaria parasite lead to particularly severe cases of the disease.

The work, which was partly funded by the EU, is published online by the journal the Proceedings of the National Academy of Sciences (PNAS).

Malaria is caused by a parasite called Plasmodium falciparum, which is transmitted by mosquitoes. After a brief spell in the liver of their human host, the parasites make their way into the
bloodstream, where they infect the red blood cells.

There they produce a protein called PfEMP1 (P. falciparum erythrocyte membrane protein-1), which sticks out of the blood cell and is able to bind with receptors on other blood cells and on the
blood vessel walls. Thus these proteins act like a glue, causing the blood cells to stick to each other and to the walls of the blood vessels.

Severe malaria occurs when large numbers of blood vessels clump together in this way and obstruct the flow of blood to vital organs such as the brain and lungs. Symptoms of severe malaria
include anaemia, respiratory problems and encephalopathy.

According to Professor Mats Wahlgren of the Karolinska Institute, who led the research, on average around 10% of malaria sufferers develop the severe form of the disease, although this figure
is higher in certain groups, including young children. The World Health Organisation states that malaria kills one child every 30 seconds.

In this latest study, the researchers studied the ‘sticky’ PfEMP1 proteins produced by parasites taken from young Ugandan children with malaria, some of whom had severe malaria.

The scientists were able to identify the parts of the protein which cause it to bond more strongly to the receptors in the blood vessels, effectively making the protein ‘stickier’. Furthermore,
these ‘sticky’ parts of the protein were more common in proteins produced by parasites taken from children with severe malaria.

The scientists are now applying their new-found knowledge to the development of a vaccine against the disease.

‘There are no vaccines yet that can prevent the development of malaria and cure a seriously infected person,’ said Professor Wahlgren. ‘We’ve now discovered a structure that can be used in a
vaccine that might be able to help these people.’

Professor Wahlgren’s team has already developed a prototype vaccine which mimics the stickiest form of the PfEMP1 protein. Tests in animals showed it to be effective at preventing infected red
blood cells from becoming ‘sticky’ and so causing the symptoms associated with severe malaria.

EU funding for the research came from the BioMalPar (‘Biology and pathology of malaria parasite’) project, which is financed under the Sixth Framework Programme’s ‘Life sciences, genomics and
biotechnology for health’ thematic area.

A year ago Professor Wahlgren’s team announced the development of a potential new drug against severe malaria called dGAG (depolymerised glycosaminoglycan). Tests in rats and primates had
showed that dGAG is effective at stopping infected red blood cells from becoming ‘sticky’ and breaking up existing clumps of cells.

Professor Wahlgren is now working with Swedish pharmaceutical company Dilafor to develop the drug further. Eventually they hope to be able to test it in humans, Professor Wahlgren told CORDIS

For more information, please visit:
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