A team of researchers from Stony Brook University has published a study that provides new insights into how the drug fexinidazole kills trypanosomatid parasites, which are responsible for diseases such as Human African Trypanosomiasis (HAT), also known as Sleeping Sickness. The findings were released in the journal PLOS Neglected Tropical Diseases.
Sleeping Sickness is caused by protozoan parasites transmitted by tsetse flies and is fatal without treatment. Existing therapies have had mixed results and can cause significant side effects. Fexinidazole, introduced in sub-Saharan Africa in 2019, is the first oral monotherapy for HAT, but until now its exact mechanism was not fully understood.
The research team, led by Galadriel Hovel-Miner, associate professor at Stony Brook University’s Renaissance School of Medicine, used advanced cell biology techniques to show that fexinidazole causes DNA damage in the parasites, leading to their death. “We found that the nuclei are aberrant in the parasites because the drug causes DNA damage, and that is the essential action that leads to death of these parasites,” said Hovel-Miner. “While the precise molecular mechanisms underlying these outcomes remain to be elucidated, our findings provide critical new insights to fexinidazole’s trypanocidal activity.”
The study also examined two other nitroaromatic drugs—nifurtimox and benznidazole—which are currently used to treat Chagas disease (American Trypanosomiasis). These drugs can be toxic and often result in poor treatment outcomes. According to Hovel-Miner: “Two of the drugs that we analyzed in this paper, nifurtimox and benznidazole, are the only drugs available for Chagas disease, and they can be toxic and have poor treatment outcomes. Therefore, fexinidazole or related drugs that kill parasites via DNA damage could prove very important as American trypanosomiasis spreads in the United States.”
Chagas disease was previously limited to South America and Central America but has recently become endemic in parts of the southern United States. The Centers for Disease Control and Prevention (CDC) reported an increase in cases as of September 2025 due to factors such as climate change making conditions more favorable for parasitic infections.
The research highlights a connection between nitroaromatic drug treatments, DNA damage formation, and reactive oxygen species activation—a process vital for parasite proliferation. The authors believe understanding these mechanisms will help develop improved treatments against trypanosomatids.
“Deconvolving the relationship between anti-parasitic drugs and the molecular basis of their cytotoxic outcomes will support future mechanistic understanding and enable improved drug design,” states their publication.
The work received funding from the National Institutes of Health (NIH), with over $500,000 awarded in 2025 and additional funds anticipated through 2027.
Research from Hovel-Miner’s lab continues to focus on identifying genetic pathways linked with anti-trypanosome therapeutics. Their discoveries are beginning to reveal links between mitochondrial stress responses within parasites and resistance to current treatments—potentially pointing toward new targets for future drug development.