An Achilles heel in malaria offers new therapy hope

Melbourne scientists have identified a chink in the life cycle of malaria that offers hope for the development of new treatment options for this devastating disease.

The malaria parasite grows inside red blood cells but to survive and cause illness it must transport hundreds of different proteins to the outside. While these proteins have many different functions that are crucial to parasite growth and survival, a common feature is that they must all pass through the same pore in the surrounding membrane.

The scientists have now discovered the identity of this protein pore. The main significance of this finding, announced today (Thursday 18 June) in the leading scientific journal Nature, is its implication for a new anti-malarial therapy.

The research has been undertaken in a collaboration that includes two of Australia's leading medical research institutes, The Burnet Institute and The Walter and Eliza Hall Institute for Medical Research and Deakin University's new Medical School.

Dr Tania de Koning-Ward, the lead author of the study and researcher with the Deakin Medical School, said the discovery opened up a new way to combat this disease.

"The next step is to identify drugs that block this protein channel. Since it is completely unique to malaria parasites this is a realistic possibility," she said.

Professor Brendan Crabb, coordinator of the project and Director of The Burnet Institute, said the discovery is a breakthrough.

"Protein export machines are of great interest in biology but because of the enormous scale of the malaria problem this one also has practical health value. Therapies that block this pore interfere with many different crucial processes in the one hit and in that sense it is an Achilles heel of the malaria parasite."

Dr de Koning-Ward will continue to characterise the components that make up this protein pore in an attempt to unravel the mechanism by which proteins are transported into the red blood cell and will move towards developing tests to screen drugs that are capable of blocking protein export as part of her growing research program at the new Deakin Medical School.

"We have recently been awarded a $315,250 grant from the National Health and Medical Research Council to continue to unravel the functional significance and contribution of protein export in malaria disease. I have been involved in researching malaria for over a decade now and it is very exciting to discover such a crucial pathway for the malaria parasite against which we can develop new therapies to treat this devastating disease," Dr de Koning-Ward said.

Malaria is spread via mosquitoes and its most lethal form is caused by the parasite Plasmodium falciparum. There are in excess of 400 million cases of malaria each year with more than one million people, mainly children, dying from the disease. New therapies are urgently needed to combat ever-increasing resistance to the available drugs.