September 25, 2018
In a study recently published in Nature Communications, Professor Leann Tilley and her team at University of Melbourne revealed how the front-line antimalarial drug artemisinin kills malaria parasites. They showed, that in a two-pronged mechanism, artemisinin damages parasite proteins and clogs the parasite’s waste disposal system, known as the proteasome, which would otherwise get rid of the damaged proteins. The damaged proteins then build up in the parasite and activate a cellular stress response that leads to parasite death.
The Tilley group have teamed up with Japanese pharmaceutical company Takeda to investigate how chemotherapy drugs targetting the proteasome can boost the efficacy of dihydroartemisinin (DHA). The team hopes to create novel analogs of human proteasome inhibitors that specifically inhibit the parasite proteasome.
According to Professor Tilley, “We want a compound that can be administered orally and will last a long time in the bloodstream. If a suitable compound can be found, human trials could happen very soon.” Parasite resistance to artemisinin and its partner drugs is spreading rapidly in South East Asia, creating an urgent call for a greater understanding of how artemisinin works, and how parasites develop resistance to the drug.
Read the Nature Communications paper here.
Model of DHA mediated killing