Old drugs could treat African Sleeping Sickness

By sorting through libraries of existing drugs, scientists have identified a subset of old medicines that may help combat a prevailing problem: the parasitic microbes that cause African Sleeping Sickness, a disease afflicting up to 500,000 people annually in sub-Saharan Africa and leaving more than 60 million at risk.

African Sleeping Sickness is a fatal disease transmitted by an infected tsetse fly. When the fly bites a human, parasitic protozoa called trypanosomes enter the bloodstream, where they multiply and ultimately wreak havoc on the central nervous system, causing motor impairment, dementia, coma and death. Drugs do exist to treat the disease, but many are too expensive or toxic to be truly effective.

“There’s a crushing need for new drug development,” says Jay Bangs, a UW–Madison microbiologist who helped scour the pharmacopia of old drugs with an eye toward new uses.

“Rather than trying to make a drug from scratch,” Bangs explains, “we’ve gone to an existing databank of compounds and found a set that may be a new class of compounds for the treatment of African Sleeping Sickness.”

Bangs and his colleague Nigel Hooper from the University of Leeds in England were interested in zinc metalloprotease enzymes, known players during the trypanosome lifecycle and implicated in mammalian hypertension and arthritis. Drugs have already been developed to block the enzyme in humans, thereby alleviating high blood pressure and inflammation; the two researchers thought those same compounds could possibly block similar enzymes in trypanosomes. By searching databases of such existing drugs, they identified a class of compounds — peptidomimetics.

“We’ve found that inhibitors of mammalian zinc metalloproteases are toxic to the parasite in quite low doses,” says Bangs. “The compounds could be used to treat diseases caused by African trypanosomes.”

That possibility, Bangs notes, is a long ways off because the peptidomimetics would need to be rigorously tested in people infected with the sleeping sickness. However, he is optimistic: “We have lead compounds and have shown they have the potential to work. There’s a whole repertoire of similar compounds that can now be tested.”

Bangs and Hooper have applied for a “concept of usage” patent, identifying a new application of the existing compounds. The patent was filed through the Wisconsin Alumni Research Foundation, a nonprofit organization that manages the intellectual property in the interest of UW–Madison.