Hope weekend rises as an international research collaborative has determined that a promising anti-malarial compound tricks the immune system to rapidly destroy red blood cells infected with the malaria parasite but leave healthy cells unharmed.
In a study by St. Jude Children’s Research Hospital scientists published in the current online early edition of the Proceedings of the National Academy of Sciences, PNAS, the researchers say the compound, (+)-SJ733, was developed from a molecule identified in a previous St. Jude-led study that helped to jumpstart worldwide anti-malarial drug development efforts.
Malaria is caused by a parasite spread through the bite of an infected mosquito. The disease remains a major health threat to more than half the world’s population, particularly children.
The World Health Organisation estimates that in Africa a child dies of malaria every minute. In Nigeria, malaria kills 300,000 children and about 4,500 pregnant women annually.
In the study, researchers determined that (+)-SJ733 uses a novel mechanism to kill the parasite by recruiting the immune system to eliminate malaria-infected red blood cells.In a mouse model of malaria, a single dose of (+)-SJ733 killed 80 percent of malaria parasites within 24 hours. After 48 hours the parasite was undetectable.
However, planning has begun for safety trials of the compound in healthy adults.
Laboratory evidence suggests that the compound’s speed and mode of action work together to slow and suppress development of drug-resistant parasites. Drug resistance has long undermined efforts to treat and block malaria transmission.
Commenting on the study, Corresponding Author, R. Kiplin Guy, Chair of the St. Jude Department of Chemical Biology and Therapeutics said: “Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose.
“These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world’s children, who are central to the mission of St. Jude.”
Whole genome sequencing of the Plasmodium falciparum, the deadliest of the malaria parasites, revealed that (+)-SJ733 disrupted activity of the ATP4 protein in the parasites.
The protein functions as a pump that the parasites depend on to maintain the proper sodium balance by removing excess sodium.
The researchers showed that inhibiting ATP4 triggered a series of changes in malaria-infected red blood cells that marked them for destruction by the immune system.
The infected cells changed shape and shrank in size. They also became more rigid and exhibited other alterations typical of aging red blood cells. Click to signup for FREE news updates, latest information and hottest gists everyday
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