A newly developed anti-malarial agent clears infections caused by the malaria parasite most lethal to humans – by literally starving the parasites to death.
The drug BCX4945 developed by researchers at Albert Einstein College of Medicine of Yeshiva University could bolster efforts to develop more potent therapies against one of the world’s leading killers.
Plasmodium falciparum, the malaria species most likely to cause severe infections and death, is very common in many countries in Africa south of the Sahara desert.
The Einstein researchers led by Vern Schramm, Ph.D., professor and Ruth Merns Chair in Biochemistry exploited what is arguably P. falciparum’s Achilles’ heel: it can’t synthesize purines, vital building blocks for making DNA.
Instead, the parasite must make purines indirectly, by using an enzyme called purine nucleoside phosphorylase (PNP) to make a purine precursor called hypoxanthine.
By inhibiting PNP, the drug BCX4945 kills the parasites by starving them of the purines they need to survive.
After BCX4945 showed potency against laboratory cultures of P. falciparum, owl monkeys were chosen as the non-human primate model for further testing of the drug.
Three animals were infected with a strain of P. falciparum that is consistently lethal without anti-malarial therapy.
Orally administering BCX4945 twice a day for seven days cleared the infections from all the animals between the fourth and seventh day of treatment. The monkeys remained parasite-negative for up to nine days post-treatment.
Parasitic infection eventually returned in all three monkeys after treatment ended, although a lower rate of parasitic growth was observed. No signs of toxicity were observed during the study period (30 days after the first dose).
“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,” he added.
The study was published in the November 11, 2011 issue of PLoS ONE.