A new study led by researchers at Stony Brook University has provided a detailed analysis of how the anti-parasitic drug fexinidazole kills trypanosomatid parasites, which are responsible for diseases such as Human African Trypanosomiasis (HAT), also known as Sleeping Sickness. This disease, if left untreated, is fatal and continues to be a significant health issue in Africa.
Fexinidazole is the first oral monotherapy developed for HAT. However, until now, its precise mechanism for killing parasites was not fully understood. The research team’s findings have been published in the journal PLOS Neglected Tropical Diseases.
Galadriel Hovel-Miner, associate professor in the Department of Microbiology and Immunology at Stony Brook University’s Renaissance School of Medicine and lead author of the study, explained that their research used advanced cell biology techniques to demonstrate that fexinidazole causes DNA damage within 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,” Hovel-Miner said. “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 compared three nitroaromatic drugs: two established treatments and fexinidazole. The results showed that fexinidazole treatment leads to an accumulation of DNA damage and inhibits DNA synthesis in trypanosomatids. This cytotoxic effect had not been clearly described since fexinidazole began use in sub-Saharan Africa in 2019.
The authors also noted a connection between nitroaromatic drug treatments and processes involving reactive oxygen species (ROS), which are important for parasite cell proliferation.
Hovel-Miner pointed out that although diseases caused by different Trypanosomatid parasites vary widely across regions and symptoms, their core biological features are similar. Understanding how drugs like fexinidazole work could help develop better treatments against these infections worldwide.
Additionally, she stated: “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 confined mainly to South America and Central America but has become endemic in parts of the southern United States according to recent reports from the Centers for Disease Control and Prevention (CDC). Warmer temperatures linked with climate change have contributed to increased prevalence of parasitic infections like Chagas disease across 21 nations including now within U.S. borders.
Research from Hovel-Miner’s lab is also exploring genetic factors behind mitochondrial stress and drug resistance among these parasites—work expected to guide future drug development efforts.
The project received more than $500,000 from National Institutes of Health funding during 2025 with additional support anticipated through 2027.
