Understanding how primaquine, an antimalarial, leads to more effective treatments for malaria

LSTM researchers have taken important steps to understand how the malaria drug, primaquine (PQ) works, which, he hopes, will lead to new, safer and more effective treatments for malaria. .

The work, which was funded primarily by a Medical Research Council award, was done by the LSTM Center for Drugs and Diagnostics (LDC). The results are published in Nature Communications.

Professor Giancarlo Biagini of LSTM:

Primaquine, an antimalarial, is the cornerstone of global efforts to eliminate malaria. For 70 years, it has been the only registered drug that has demonstrated its ability to cure recurrent malaria and block the transmission of the disease. However, the mode of action of this drug was still poorly understood, seriously compromising efforts to improve the safety and pharmacology profile of this important clbad of drugs. "

The LSTM team, in collaboration with key collaborators such as Professor Paul O'Neill (University of Liverpool), Professor David Baker (School of Hygiene and Tropical Medicine London) and Professor Sangeeta Bhatia ( Mbadachusetts Institute of Technology, USA) was able to replicate the interaction between drug and host enzymes that catalyze the production of cytotoxic amounts of hydrogen peroxide from PQ metabolites. The experiments demonstrated why the drug exhibited exquisite selectivity for specific parasite stages and also explained why only very small catalytic concentrations (nM) of metabolites were required to kill the parasites.

The search for new antimalarials is vital for the global elimination of malaria, especially since PQ is potentially fatal for people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disease that affects millions of people in malaria endemic countries.

"That's why it's essential to understand how the drug works to reproduce its most significant elements." Continuing Professor Biagini: "This work was possible with CDD given the multidisciplinary nature of the team. This study represents a significant advance in our understanding of the mechanism of action of the PQ. This new knowledge is essential for the development of new, safer, broad-spectrum antimalarial drugs, work in progress in our group. "