Breakthrough in the Fight Against Malaria: MED6-189

In 2022, nearly 619,000 global deaths resulted from malaria caused by Plasmodium falciparum, the most virulent and deadly malaria parasite. Resistance to all existing antimalarial drugs poses a significant challenge, prompting researchers to seek innovative remedies. This is prepared by SSP.

A collaborative effort involving scientists from UC Riverside, UC Irvine, and Yale School of Medicine has led to the development of a groundbreaking new drug, MED6-189. This drug has demonstrated efficacy against both drug-sensitive and drug-resistant strains of P. falciparum in laboratory tests and humanized mouse models engineered to contain human blood.

Reported in the journal Science, MED6-189 disrupts both the apicoplast (an organelle in P. falciparum cells) and vesicular trafficking pathways, thereby preventing the pathogen from developing resistance. This dual approach makes the drug a highly effective antimalarial agent and a promising new lead in the battle against malaria.

Professor Karine Le Roch, a senior author from UC Riverside, states that disrupting these pathways blocks parasite development, eliminating infection in red blood cells and humanized mouse models. Additionally, MED6-189 shows potency against other zoonotic Plasmodium parasites such as P. knowlesi and P. cynomolgi.

MED6-189 is a synthetic compound inspired by marine sponge extracts, synthesized by Christopher Vanderwal's lab at UC Irvine. According to Vanderwal, many leading antimalarial agents originate from natural products. MED6-189 resembles isocyanoterpenes, a class of natural products that target multiple pathways in P. falciparum, reducing the likelihood of resistance.

Further research efforts by GSK in Spain demonstrated that MED6-189 eradicates the parasite in infected mice. Collaborating with Choukri Ben Mamoun of Yale School of Medicine, the team also validated the drug's efficacy against P. knowlesi in monkey-infected red blood cells.

Looking ahead, the researchers aim to optimize MED6-189 further and confirm its mechanisms of action through a systems biology approach, which allows a comprehensive understanding of the biological systems and interactions at play.

The coordinated efforts of the team, supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, along with the continued research at institutions like the Stowers Institute for Medical Research and the University of Georgia, show great promise in the pursuit of effective malaria treatment.