A Golden Cure for the 'Baghdad Boil'?

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Unhealing Ulcers Afflict Millions, Including U.S. Troops; UVA IDs Promising Treatment

There are neglected diseases, and this is one of the most neglected of the neglected diseases.

A protozoan parasite that causes unhealing, potentially disfiguring skin sores appears to have a weakness for gold.

Researchers have discovered that an existing gold-based drug is toxic to the microscopic parasite that causes the disease known as cutaneous leishmaniasis, a condition that affects millions, including U.S. troops. The discovery is notable because there is no reliable treatment for the disease, as existing treatments are inconsistently effective or act by a mechanism that is poorly understood. These treatments can be extremely painful, as they are usually injected directly into an open sore, and sometimes can prove fatal.

“There are neglected diseases, and this is one of the most neglected of the neglected diseases,” said Elizabeth R. Sharlow, PhD, of the University of Virginia School of Medicine, the lead author of a new paper outlining the leishmaniasis discovery.

“Neglected disease drug discovery is a niche that academic health systems have, and it’s an important one,” said collaborator John S. Lazo, PhD, of the School of Medicine.

Unhealing Ulcers
It’s estimated that approximately 1.5 million people in 98 countries are stricken with cutaneous leishmaniasis each year, primarily in the Middle East, tropical Africa and parts of Asia. U.S. troops stationed in Iraq and Afghanistan have contracted the disease, dubbing it the “Baghdad boil.” Mexico and parts of South America are affected as well, as are several regions in the U.S. The disease is transmitted to humans by the bite of sandflies.

UVA’s research was done in collaboration with the Walter Reed Army Institute of Research. By screening a relatively small library of existing drugs – a few thousand, rather than tens or hundreds of thousands – the researchers determined that the drug auranofin and potentially its derivatives are effective against leishmaniasis. “This screening process greatly shortens the discovery and development time required,” Sharlow said. “Taking a drug that’s already been carefully looked at and repurposing it for something else is quite attractive for these types of diseases.”

Leishmaniasis Treatment
Auranofin is based on gold but the researchers believe it would not be that expensive to produce for leishmaniasis treatment. And that’s an important consideration for a new treatment for the disease. “Leishmaniasis occurs in a lot of countries where people are quite poor, so an inexpensive drug is paramount,” Lazo said.

The research has shown the arthritis drug to be effective against the cutaneous form of leishmaniasis, which affects the skin, and the researchers hope it will prove effective against the potentially deadly visceral form that affects internal organs.

‘Monumental’ Discovery
While more research needs to be done before auranofin can be used as a treatment for leishmaniasis, UVA’s Richard Pearson, MD, one of the nation’s top experts on the disease, hailed the findings as a major breakthrough. “The problem has been that we’ve not had a very good arsenal of drugs. For cutaneous disease, standard treatments are very expensive and you have to put an IV in and give it multiple times,” Pearson said. “That’s why the work is so significant here. We really need a safe, oral drug that’s well tolerated. … This discovery is monumental. It’s cutting-edge and provides great hope for the future.”

Published Online
The findings have been published online by the journal ACS Chemical Biology and will appear in a forthcoming print edition. The article was authored by Sharlow, Stephanie Leimgruber, Samantha Murray, Ana Lira and Lazo, of UVA’s Department of Pharmacology; Richard J. Sciotti, Mark Hickman, Thomas Hudson, Susan Leed, Diana Caridha and Max Grögl, of the Walter Reed Army Institute of Research; Amy M. Barrios, of the University of Utah; and David Close, of the University of Pittsburgh.

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