Administering drug treatments while parasites are less active may be the best way to put a deadly disease to rest.
UT Southwestern researchers discovered that the parasitic worm responsible for African sleeping sickness, Trypanosoma brucei, is more susceptible to drug treatments during the later hours of the evening. Filipa Rijo-Ferreira, the study’s lead author and neuroscience postdoc, and Joseph Takahashi, neuroscience chair, published their research in Nature Microbiology.
“We treated the parasite at different times throughout the day and discovered that there is a certain timing at which (the worms) are more sensitive to the treatment, which was quite unexpected prior to this research,“ Rijo-Ferreira said.
Rijo-Ferreira said the team began by studying the worm inside and outside of the human body to determine if the worm had its own circadian rhythm. Circadian rhythms regulate sleep cycles and other bodily functions, such as hunger and body temperature, in humans and other animals, Takahashi said. The Trypanosoma brucei has similar rhythms to the humans where they reside, which Rijo-Ferreira said has implications for the parasite’s survival.
“When we eat, the parasite is awake and also gets the nutrients that we receive, it’s a really important mechanism, because the parasites know what time it is within our bodies, and can anticipate the timing of our biological events,” Rijo-Ferreira said.
Rijo-Ferreira said the team created an environment similar to that of the human body to study the worm without the need for a human host.
“(Human body) temperature is lower at night when we are sleeping, and a little higher during the day when we are active, so we try to simulate the temperature cycles of a host while the worm is (inside the body),” Rijo-Ferreira said.
Rijo-Ferreira said that when organisms need to perform functions such as eating, sleeping or preparing to fall asleep, the genes responsible for these functions become activated, or ‘expressed,’ at different levels. She said these genes are typically expressed more during daylight hours than at night.
As the team cycled the temperatures of the worm’s environment to mock that of a human body, the scientists monitored the amount of genes that the worm expressed for functions such as hunger and body temperature.
Takahashi said researchers found the worm expressed the same pattern of genes, regardless of changes in the temperature of its environment. He said this means the worm has its own circadian clock and is not relying on its host.
Rijo-Ferreira said one gene that appeared to be solely controlled by the worm’s circadian rhythm was responsible for the parasite’s metabolism.
She said current anti-sleeping sickness drugs work by harnessing the parasite’s metabolic system, meaning the drug is processed within the parasite. She added that the team was able to determine that the drugs are more effective when administered in the later hours of the day, when the metabolic system is less active and its genes are less expressed.
In the future, the team hopes to find a way to control the parasite’s own circadian rhythm and diminish its activity to make the parasite less intrusive.
“We should figure out how to block (the parasite’s) ability to anticipate these actions within a host and further administer drug treatments more effectively for this disease and others ones,” Rijo-Ferreira said.
