Professor Alan Cowman
About the talk:
Artemisinin combination therapies (ACTs) are the main treatment option for malaria, caused by the intracellular parasite Plasmodium spp. However, increased resistance to ACTs highlights the importance of finding new drugs with novel modes of action. Recently, the aspartic proteases Plasmepsin IX and X (PMIX and PMX) have been identified as promising drug targets. We have built a drug discovery program with the pharmaceutical company Merck to develop dual inhibitors of PMIX and PMX that block multiple stages of the Plasmodium lifecycle. Using these chemical tools we have shown that PMX and PMIX are master modulators for P. falciparum invasion of human erythrocytes and for maturation of proteins required for parasite development and egress from the host cell. These compounds show in vivo and in vitro efficacy against all Plasmodium spp. tested. Dual-PMIX and PMX inhibitors are promising candidates for malaria treatment and prevention as oral administration of our lead compound cures mice of P. berghei and is also efficacious against P. falciparum asexual infection in humanised mice and prevented transmission to mosquitoes. These compounds have a very high bar for the ability of the malaria parasite to develop resistance. The dual PMIX and PMX inhibitors have been developed for use in treatment for multi-drug resistant malaria infections.
About the speaker: Alan F. Cowman AC FRS FAA is Deputy Director at WEHI. He did his undergraduate degrees at Griffith University followed by a PhD at WEHI. After a two-year postdoctoral fellowship at UC- Berkeley he returned to WEHI and developed a laboratory studying malaria. He has worked on malaria for 30 years and published over 330 papers on infection and pathogenesis to understand the function of proteins in Plasmodium falciparum, the causative agent of the most severe form of malaria. The aim of his laboratory is to develop vaccines and drug targets against this parasitic disease and has major collaborations with the pharma including Merck USA and Janssen.Please let me know if you have any questions.
Read more about Prof Alan Cowman’s work here