New Area in Malaria
Development of malaria therapeutics has been stymied by poor understanding of drug targets and limited corporate interest in picking up preclinical compounds with therapeutic promise. At the same time, the parasite has shown mounting resistance to older drugs, making drugs against new targets ever more urgent.
Now, a trio of articles describes a range of drug discovery approaches that may yield new types of antimalarial agents.1-3 The proof-of-principle compounds identified in the studies are not yet ready to enter the clinic, but they could serve as starting points for designing improved compounds using SAR analysis, according to the authors.
With clinical testing infrastructure already in place from previous trials and financial incentives available from not-for-profits such as Medicines for Malaria Venture (MMV), the challenge for industry is to advance the new compounds through the bottleneck of corporate preclinical development into not-for-profit-sponsored clinical testing programs.
The studies take contrasting approaches to finding new compounds and target distinct steps in the complex life cycle of Plasmodium falciparum, the protozoan parasite that causes about 80% of malaria cases. (The other 20% of cases are caused by other Plasmodium parasites.)
P. falciparum's life cyclehas several windows of vulnerability to therapeutics.
After initial human infection, parasites spend much of their time inside red blood cells, feeding on hemoglobin. The bugs replicate in theimmunological safe haven of