Zachary Mackey is trying to deliver a stern wake-up call to the parasite that causes sleeping sickness, a neurological disease that threatens millions of lives in 36 countries in Africa, according to the World Health Organization.
Mackey identified a protein vital to the sleeping sickness parasite’s good health. Disrupting the protein with drugs could potentially make it impossible for the parasite to reproduce and survive, and thereby reducing its danger to human health.
The discovery suggests multiple ways to disrupt the protein’s function, said Mackey, an assistant professor of biochemistry in the College of Agriculture and Life Sciences, an affiliated faculty member in the Fralin Life Science Institute, and an affiliated researcher in Virginia Tech’s Vector-Borne Disease Research Group.
Sleeping sickness is caused when the vector-borne parasite Trypanosoma brucei crosses the blood-brain barrier during the late stage of infection.
The native African tsetse fly transmits the parasite through a painful bite, allowing it to spread through the body, causing fever, headache, and intense aches and pains.
When the parasite spreads to the brain, it causes swelling, slurred speech, confusion, and difficulty walking, followed by coma and eventually death.
Mackey thinks that overexpressing, depleting, or blocking the protein — known as proliferating cell nuclear antigen — represents three ways this protein could be targeted in the parasite, broadening the types of small molecules or drugs that can be developed to treat the disease.
Though a few drugs currently exist, they are either very expensive or have extremely powerful side effects due to their toxicity, according to Mackey, who is also an affiliated researcher in the Virginia Tech Center for Drug Discovery.
Mackey now investigates how altering the amount of protein kills the parasite. Once he better understands how this protein regulates the parasite’s life cycle, he can partner with chemists to synthesize small molecules that target the protein’s disruption.