Penn researcher developing new treatments for neglected tropical disease

Leishmaniasis is far from a household word in the United States, but in the tropics, this disease affects roughly 12 million people, with about 2 million new cases every year. The cutaneous form causes unsightly skin ulcers that take months or even years to heal, and can cause major tissue damage.

“There is no vaccine and the drugs that are used to treat this disease are not very effective and can be quite toxic,” says Phillip Scott, vice dean for research and academic affairs and a professor of microbiology and immunology at Penn’s School of Veterinary Medicine.

Scott is part of an effort to overcome these obstacles. Working both in his lab at Penn and in a clinic in Brazil, Scott and his colleagues are making insights into the basic biology of leishmaniasis that may give rise to new treatments that are both safe and effective.

Leishmaniasis is caused by a parasite transmitted by the bite of a sand fly. Upon entering the skin, the parasite infects and then replicates inside the body’s macrophages, the immune cells that would normally be responsible for killing such invaders.

Over the last 30 years, Scott has worked to understand how the immune system responds to leishmania infections. An element of the disease that has particularly puzzled him and others is that some patients have very low levels of the parasite and show evidence of a strong immune response, but still have extremely severe cases of the disease. This scenario is particularly common in parts of Brazil, where Scott has worked in a clinic that sees about 1,500 leishmaniasis patients each year.

Through experiments in both mice and patients, Scott found that a form of the immune system’s T cells, called CD8 cells, can in some cases help clear leishmania infection. But other times, these cells actually exacerbate disease by popping open macrophages, allowing the parasite to spread and promoting inflammation. Understanding what factors determine whether CD8 cells are helpful or harmful may one day lead to a leishmaniasis vaccine or new therapies.

As a first step, Scott is involved in designing a clinical trial for patients at the Brazilian clinic to test an inflammation-blocking drug called anakinra in treating stubborn leishmaniasis infections. Anakinra is already used to treat rheumatoid arthritis, so it is known to be safe.

“In our animal model, we’ve already shown that we can cure disease,” Scott says. “Most tropical diseases don’t get the attention of drug companies, so if we can use a drug that is already available to effectively treat leishmaniasis, it’s a win-win.”

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