A new research has developed specific, potent drugs against Chagas disease and sleeping sickness.
These diseases, caused by Trypanosoma protists, infect millions of people and livestock worldwide taking lives and cause severe economic losses. Existing drugs against the bugs are fast becoming ineffective and have serious side effects.
Scientists targeted small compartments – called the peroxisome – in Trypanosoma cells to kill these pathogens. The peroxisome performs essential metabolic functions in Trypanosoma cells to keep it alive. These cellular compartments are also present in humans, plants, fungi and nematodes. In humans, dysfunctional peroxisomes cause Zellweger syndrome and related diseases that may cause early deaths.
The research, published in a leading scientific journal Science, targeted a unique feature in Trypanosoma peroxisomes to create highly specific drugs that show low toxicity in human cells.
Importing enzymes into the peroxisome is vital for it to perform its function. If the peroxisome is unable to perform its function the organism is likely to die due to the build-up of toxins. The study also shows that the peroxisomes are attractive targets for drug design against fungi and nematodes. These organisms also cause severe diseases in plants, animals and humans.
The drugs target Trypanosoma PEX14 protein, which is required to import enzymes into peroxisomes, and deactivates the function of PEX14, which means peroxisomes become dysfunctional and leading to the death of the organism. These drugs have the potential to become candidates against Trypanosoma pathogens in a clinical trial.
Click here to read the article: “Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites, Dawidowski et al., Science 355, 1416–1420 (2017)”.