New anti-malaria compound destroys parasite quickly

One of the challenges in the fight against malaria - a disease that threatens half the world's population and kills a child in Africa every minute - is that it rapidly becomes resistant to new drugs. 

To sustain their effectiveness, new drugs need to act fast and eliminate the parasite before it has a chance to develop resistance. Now, a new study offers such a compound - in mice it removed all traces of malaria parasite within 48 hours.

Within 48 hours of receiving a new compound that tricks the immune system into destroying only infected red blood cells, malaria-infected mice showed no traces of the parasite.

The study, which was conducted by an international team led by researchers at St. Jude Children's Research Hospital in Memphis, TN, is published in the Proceedings of the National Academy of Sciences.

Malaria is a disease that develops when a mosquito infected with a Plasmodium parasite bites a person. Once it gets into the bloodstream, the parasite invades and lives in the new host's red blood cells.

According to the World Health Organization (WHO), malaria killed an estimated 627,000 people in 2012, the majority of them sub-Saharan African children under the age of 5.

(+)-SJ733 - the compound tested in the new study - tricks the host immune system into destroying only infected red blood cells while leaving healthy ones alone.

The new compound is a derivative of one identified in a previous St. Jude-led study that helped spur worldwide anti-malaria drug development projects.

New compound disrupts malaria parasite's internal sodium balance

The researchers found (+)-SJ733 uses a previously unknown mechanism to kill the parasite.

After whole genome sequencing the deadliest malaria parasite species - Plasmodium falciparum - the international team discovered that (+)-SJ733 disrupts activity of the ATP4 protein in the parasite.

ATP4 is a sodium-removing pump that the parasite relies on to maintain sodium balance in its single, protozoan cell.

In their study, the team showed that giving a single dose of (+)-SJ733 to malaria-infected mice killed 80% of the parasites within 24 hours. Furthermore, the parasite was undetectable after 48 hours.

Results suggests new compound suppresses malaria drug-resistance

The researchers suggest their lab results show (+)-SJ733 both slows and suppresses the development of drug-resistant malaria parasites.

The research team at the St. Jude Department of Chemical Biology and Therapeutics, says, their goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose.

The team now plans to carry out safety trials of the compound in healthy human adults.

Grants from various bodies, including the National Institutes of Health, Medicines for Malaria Venture, Australian National Health and Medical Research Council, and the Howard Hughes Medical Institute helped fund the study.

Meanwhile, we recently learned and published earlier another breakthrough in the fight against malaria, where researchers found good gut bacteria to be highly effective against malaria. In that study, the team discovered certain bacteria in the gut may induce a natural antibody defense against the infection. They also found children tend not to have enough of the antibodies to stave off malaria.

References:

(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium, María Belén Jiménez-Díaz et al., PNAS, doi:10.1073/pnas.1414221111, published online 1 December 2014, abstract.
St. Jude Children's Research Hospital news release accessed 8 December 2014.