Malaria is a global infectious disease that remains a leading cause of morbidity and mortality in the developing world. In a recent breakthrough, researchers have shown that a promising new antimalarial treatment is effective against both drug-sensitive and drug-resistant malaria parasites in laboratory and mouse studies.
The parasite studied was Plasmodium falciparum, which is a unicellular protozoan parasite of humans. It is regarded as the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of an infected female Anopheles mosquito. P. falciparum is highly prevalent in Africa, South-East Asia, Eastern Mediterranean, and Western Pacific regions.
There is a finite number of antimalarials together with limited protection offered by current vaccines. Hence, there is an urgent need for therapeutics to suppress the spread of the disease.
The isocyanoterpene (ICT) family of sponge-derived natural products has potent antibacterial, antifungal, and antimalarial activity. Terpenes are volatile, unsaturated 5-carbon cyclic compounds, which are built up of isoprene monomeric units.
Among the ICTs, the kalihinol subfamily, including kalihinols A and B, shows activity against drug-sensitive and drug-resistant P. falciparum isolates.
Since the large-scale biological production of the kalihinol derivatives is complex, the researchers chemically synthesized kalihinol analogs. This allowed for the development of a highly potent drug.
This experimental treatment, coded MED6-189, is based on the compound found in marine sponges (simple aquatic animals that possess dense, yet porous, skeletons). The study primarily comes from researchers at the University of California-Riverside, UC-Irvine, and the Yale School of Medicine.
The drug MED6-189 disrupts the lifecycle of the parasite, slows its growth, and kills it. This occurs as MED6-189 targets the apicoplast, which is a nonphotosynthetic plastid found in the parasites (inhibiting lipid biogenesis and cellular trafficking).
The research team is hoping to gain approval to test the treatment in a Phase 1 clinical trial to evaluate it for safety and side effects.
The research appears in the journal Science, titled “A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria.”
