One of many. A patient in Uganda receives one of the 56 doses of eflornithine needed to treat African sleeping sickness.

Andy Crump/WHO/TDR

Hitting Sleeping Sickness Where It Lives

African sleeping sickness is one of the most neglected of the neglected diseases. But thanks to a new collaboration, researchers have crafted a compound that kills the parasites that cause sleeping sickness in the blood and the brain. After promising studies in rodents, the compound will enter human safety trials later this year.

Human African trypanosomiasis (HAT), the formal name for the disease, sickens an estimated 30,000 people per year. The culprits are two subspecies of the microscopic parasite Trypanosoma brucei. Injected by the bite of the tsetse fly, the invaders first dwell in the blood and then infiltrate the brain, causing confusion, hallucinations, lethargy, and other symptoms. Untreated HAT is fatal, but treatment can be as well. The drug mainstay, melarsoprol, contains arsenic and kills one in 20 people who take it. A newer medicine, eflornithine, isn’t as harsh but is complex to dispense, requiring four intravenous infusions per day for 2 weeks.

This bleak situation could be starting to change. Last year, a team led by scientists at the University of Dundee in the United Kingdom reported synthesizing a molecule that killed sleeping sickness parasites in the blood of mice, although it couldn’t enter the brain. Other scientists have resurrected fexinidazole, a compound tested as an antimicrobial in the 1970s and '80s but never developed into a drug. Phase I safety trials of fexinidazole in people recently concluded.

In the latest discovery, biotech company SCYNEXIS in Research Triangle Park, North Carolina, and Anacor Pharmaceuticals in Palo Alto, California, combined forces to design and test potential medications. Sponsoring their collaboration was the Drugs for Neglected Diseases initiative, a nonprofit organization based in Geneva, Switzerland.

As researchers report online today in PLoS Neglected Tropical Diseases, the compound they developed, known as SCYX-7158, slays both subspecies of the parasite in the lab dish. Tests in mice, which also fall victim to the illness, showed that SCYX-7158 killed the parasites in the blood and saved the animals. By contrast, untreated mice typically died within 4 to 5 days. The researchers also found that the compound entered the brain. It cured mice even when the trypanosomes had settled there, suggesting it works against the late stage of the disease.

Because patients would take the compound orally, treatment would be relatively easy. If SCYX-7158 pans out in further trials, “it will be the first new, orally active treatment for sleeping sickness in the past 30 years,” says Robert Jacobs, a medicinal chemist at SCYNEXIS and lead author on the new study. Plans call for the safety trials to start in Paris later this year, he says.

Parasitologist Simon Croft of the London School of Hygiene and Tropical Medicine says that the research is important. “I think it offers some hope for the future, but there’s still a long way to go.” For one, researchers still need to determine if the compound is safe and works in people.