A quick, often imperceptible bite from a sand fly can transmit the dreaded parasitic disease leishmaniasis. No vaccine exists for the infection, which causes disfiguring and long-lasting skin ulcers.

“This is a neglected tropical disease, so it can be difficult to get the investment needed to develop new therapies,” says Phillip Scott, vice dean for research and academic resources at the School of Veterinary Medicine.

Fortunately, new findings by Scott, research associate Fernanda Novais, and colleagues suggest that drugs currently approved by the FDA for combating other conditions may be able to perform double duty as leishmaniasis therapies.

The researchers made the discovery, published in the journal PLOS Pathogens, by examining the molecular pathway that leads to the inflamed skin lesions. From decades of earlier investigations, they knew that the inflammation owed less to the direct effect of the parasite than to the activity of CD8 T cells.

“In earlier work, we found that CD8 T cells lead to inflammation, but what we didn’t know was what was downstream from the CD8 T cells,” Novais says.

The researchers began by following up on a suspect from an earlier study, the cytokine IL-1b. They had found the gene for this protein at elevated levels in biopsies of lesions from leishmaniasis patients.

In mice, they found higher levels of IL-1b in immune-deficient animals with leishmaniasis that had CD8 T cells added back than in infected, immune-deficient animals without the CD8 cells.

Treating the mice with CD8 cells using an inhibitor of IL-1b greatly reduced the severity of their disease. Treatment with the drug anakinra, which blocks the IL-1 receptor, was also effective.

Further experiments revealed that a molecular complex upstream of IL-1b, which is required for processing the cytokine, was also important in causing the skin lesions. Inhibitors of this complex, the NLRP3 inflammasome, were effective at preventing severe disease in mice. One of these inhibitors, glyburide, is currently FDA-approved as a diabetes treatment.

In a final set of tests, the researchers found that the same molecular pathway was active in human tissue samples, suggesting that the efficacy seen in mice may successfully translate to human patients.

To confirm this, the researchers hope to follow up with clinical trials testing one or more of the drugs currently on the market, such as anakinra, glyburide, or a humanized inhibitor of IL-1b, against leishmaniasis in people.