Starving the malaria parasite to death shows real promise as cure

Malaria is one of the world’s largest killers of human beings. In 2008 there were between 190 million and 311 million reported cases of malaria with between 708,000 and 1.003 million people killed by malaria; with the majority of those deaths occurring in sub-Saharan Africa.

A new study published in the November 11, 2011 issue of PLoS ONE reports about a new line of attack against malaria that is showing real promise.

Discovered by researchers at Albert Einstein College of Medicine of Yeshive University this new antimalarial agent is proving effective at clearing infections caused by malaria parasite by simply starving the parasites to death.

This “starving” can be done because of a weakness that the researchers found with strain of the parasite most commonly associated with severe infections and death – the Plasmodium falciparum (P.falciparum) strain. The “Achilles heel” as the researchers call it is that the P.falciparum can’t synthesize a vital building block for making DNA called purines.

Instead the parasite makes these purines by indirect methods by using an enzyme called purine nucleoside phosphorylase (PNP) to make the needed purine precursor called hypoxanthine. This is the point that the researchers have targeted as the weak point and by using the drug BCX4945 they kill the parasites by starving them of the purines they need.

The transition-state analog BCX4945 was chosen for this study because of its high affinity for both P. falciparum PNP and human PNP (which the parasite obtains from the red blood cells it infects). Since PNP is abundant in mammalian red blood cells and those cells are constantly replaced, BCX4945 is toxic only to the parasite and not its mammalian hosts. (Two of Dr. Schramm’s other PNP inhibitors — one for T-cell cancers, the other for gout — are being evaluated in clinical trials.)

“Inhibiting PNP differs from all other current approaches for treating malaria,” said Dr. Schramm. “For that reason, BCX4945 fits well with the current World Health Organization protocols for malaria treatment, which call for using combination-therapy approaches against the disease.”

via Science Daily

image courtesy of Doctors Without Borders