$16 Million to Fight Childhood Mortality, River Blindness in Africa

Thomas Lietman, MD, treats a young boy in Matameye, Niger, in 2012. Lietman is leading a team that’s received $12 million for a multi-year trial to study the effectiveness of the antibiotic azithromycin in reducing childhood mortality in Niger, Tanzania and Malawi.

Two UCSF teams have received a total of $16 million from the Bill & Melinda Gates Foundation to study new ways to significantly reduce childhood mortality and disease in developing nations. An international team led by Thomas M. Lietman, MD, associate director of the UCSF Francis I. Proctor Foundation for Research in Ophthalmology, received $12 million for a multi-year trial to study the effectiveness of mass oral administration of the antibiotic azithromycin in reducing childhood mortality in Niger, Tanzania and Malawi – three nations with severe childhood mortality rates. A second team, led by James H. McKerrow, MD, PhD, professor of pathology and pharmaceutical chemistry, received $4.3 million to identify and develop a drug that kills the parasitic roundworms known as filiariae that cause river blindness, the leading cause of blindness in parts of West Africa. If successfully developed, the same drug will have a high probability of killing the closely related parasite that causes lymphatic filariasis, or elephantiasis, a crippling and disfiguring disease that affects millions of people in Africa, Asia, the Indian subcontinent and South America. Lietman’s project is based on an earlier study in which communities in Ethiopia that received mass doses of azithromycin to treat trachoma – a strain of chlamydia that causes blindness – experienced an overall reduction in childhood mortality from all causes. Community-wide antibiotic administration is common in African nations where trachoma is usually found, he said. Preschool children in Lietman’s study will be randomized to receive either a cherry-flavored oral suspension of azithromycin or a placebo every six months for two years. If there is a significant reduction in mortality in the communities that receive the antibiotic, the study will be extended for another two years and all communities will receive antibiotics. The goal of McKerrow’s study is to find a drug that kills the adult form of the parasitic filarial worm, which is spread by a fly that breeds near fast-flowing rivers. When the fly bites, it deposits larvae under the skin that grow into worms several inches long. The parasite associated with river blindness attacks the eye, while its relative that is responsible for lymphatic filariasis blocks the lymphatic channels in the groin, resulting in extreme swelling of the lower extremities. McKerrow’s research group will employ new software developed by UCSF research specialist Chris Marcellino that significantly speeds the screening of potential compounds. Conventional drug screening technology uses plates with many hollows, or wells, each of which contains a candidate compound that is screened individually for promising activity. The new software allows an entire plate to be scanned for results in seconds. Scanning and evaluating a whole plate rather than individual wells is necessary, McKerrow explained, because of the large size of the worms, which restrict each plate to dozens rather than hundreds of wells. “With conventional, well-by-well scanning, it would take a long time to screen many compounds,” said McKerrow. “But if you can scan a whole plate and then move on to the next plate in a few seconds, you can filter through thousands of compounds much more efficiently.” The compounds will come from two sources. The first is what McKerrow calls traditional drug discovery, which starts from chemicals that aren’t yet drugs. That research will take advantage of unique chemistry developed by Bay Area biotech company Anacor Pharmaceuticals. The second source is “repurposed drugs” that have already been approved by the FDA for human use. Working in collaboration with the UCSF Small Molecule Discovery Center, McKerrow’s group expects to create a library of approximately 1,700 FDA-approved drugs that can be used in this and similar screens. – By Kristen Bole, UCSF
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