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If a picture is worth a thousand words, photos of leishmaniasis patients speak volumes of suffering: a disease that leaves disfiguring skin lesions that scar for life, requiring painful, burning injections or IV infusions to cure. “They’re almost a form of torture,” Scott Schaus says of the treatments.
A team including Schaus (CAS’95), a College of Arts & Sciences associate professor of chemistry and a School of Medicine associate professor of pharmacology, and Lauren Brown, a CAS research assistant professor of chemistry, has developed a process that a major pharmaceutical company says might yield better drugs against leishmaniasis, a sand fly–borne illness afflicting 12 million people worldwide, with 2 million new cases reported each year. Brown and Schaus are among eight winners of GlaxoSmithKline’s (GSK) first Discovery Fast Track Competition, which seeks promising ideas for future drugs.
The team identified compounds, developed at BU’s Center for Molecular Discovery, that are effective against 2 of the 15 species of the leishmania parasite.
There is no cash award from the competition—which drew almost 150 applicants—but winning means GSK is “interested in working with us further to develop potential drugs to be able to treat the disease,” says Schaus. The collaboration will also include University of California, San Francisco, colleagues James McKerrow and Jair Lage de Siqueira-Neto, of the Center for Discovery and Innovation in Parasitic Diseases, who screened the compounds and found them effective in lab mice. They have “the expertise in dealing with parasitic and infectious disease,” says Schaus. “BU has the chemistry expertise to be able to develop compounds that are effective. GSK has the drug development expertise to be able to move this forward.”
Hypothetically, if all goes well, drugs could be available for clinical trials within five years, but “a lot of things remain to be determined” first, says Brown. The researchers and GSK must determine that the compounds work in, and are not toxic to, humans. “Ideally, we would want to be developing a drug that would be a pill,” less painful and easier to distribute than the injections or IV treatments currently used, she says.
“Your direct ‘line of sight’ to a medicine was compelling,” GSK said in its letter of commendation to the BU team. It also cited their collaboration with McKerrow, holder of the Robert E. Smith Endowed Chair in Experimental Pathology, whose center guarantees access to vital lab facilities.
Leishmaniasis is found in tropical and subtropical regions as well as in southern Europe, although cases have been reported in Texas and Oklahoma. Three-quarters of new cases are cutaneous, meaning the victims get skin sores. The remaining cases are visceral (affecting internal organs such as the liver, spleen, and bone marrow), and that form of the disease is lethal if untreated. Existing drug treatments, in addition to being painful, are either expensive or potentially toxic, requiring a doctor’s monitoring during use.
The BU researchers aren’t the only ones looking for better treatments; a Food and Drug Administration advisory panel has recommended approval of an experimental drug from Paladin Labs to treat cutaneous leishmaniasis. But Brown and Schaus say that drug, currently being used in India particularly, is having diminishing effectiveness, as the disease can mutate to become drug-resistant, with increasing incidence of relapse.
Countries typically try to prevent the disease by spraying insecticides, but Schaus says that geopolitical unrest often interrupts spraying, resulting in outbreaks. The civil war in Syria is a case in point—the cutaneous disease there is called “Aleppo buttons,” referring to the region where an estimated 100,000 new cases have been reported since the strife began, according to Schaus. He says Darfur and South Sudan suffered a fourfold increase in visceral cases among displaced refugees.