Schistosomiasis, a devastating parasitic disease thought to have infected Napoleon and his troops by frequenting Egyptian baths, is one of the five “neglected diseases of mankind” identified by the World Health Organization (WHO), along with Chagas’ disease, African sleeping sickness, chloroquine-resistant malaria, and leishmaniasis. These diseases kill hundreds of millions of people each year, but because their victims are among the world's poorest, they have not engaged the interest of the pharmaceutical industry.

"So we decided to develop our own drug company within the university," says McKerrow.

The effort comes on the heels of a report from Medicins Sans Frontieres (Doctors Without Borders), who in 2001 cited the Western profit motive model as the key factor behind the pharmaceutical industry’s neglect, and called for the public sector to take a needs-based approach to managing drug development.

“If this were cancer or heart disease, major drug companies would be knocking on our door once we identified a new drug target,” says McKerrow. “Because no one came knocking, we decided to fill in that gap.”

First success

Their first success has been CRA-3316, a cysteine protease inhibitor that kills the parasite Trypanosoma cruzi, which infects its victims with Chagas’ disease. Named for Brazilian physician Carlos Chagas, who first described it in 1909, the condition is the leading cause of heart disease in Latin America. Sixteen million people are affected, and about a quarter of the population of Latin America is at risk of developing the disease. The disease is such a renowned local scourge that an illustration of Chagas and even the T. cruzi parasite appears on Brazilian currency.

The disease is directly linked to poverty. The crevices of adobe walls and thatch roofs in many poor rural homes provide a thriving habitat for the blood-sucking triatomine bugs that transmit the parasite. With the rural-to-urban migration of the 1970s and 80s the epidemiological pattern shifted into an urban infection transmitted by blood transfusion; contamination of blood supplies in various parts of Latin America have been estimated to be as great as 50% - higher than local contamination rates for either HIV or hepatitis B and C.

A course of therapy was developed for Chagas’ disease 30 years ago, but according to McKerrow is “so toxic almost no one completes it - anything we could come up with would be better than what's out there."

The research has been made possible by the Sandler Center for Basic Research in Parasitic Diseases, established in August 2001 by a generous grant from the Sandler Family Supporting Foundation. The center’s founding mission is to address the global impact of diseases that affect hundreds of millions of people in poverty.

A collaborative approach

The center formalizes the collaboration of a number of scientists from different disciplines – including biologists, synthetic chemists, and computer scientists - who had already been working together for nearly a decade.

“UCSF is unique in having scientists from different disciplines collaborating – that’s how we work,” says McKerrow. “In another institution, scientists from different disciplines would be set off in their own building or lab, and people would compete for space and staff. Here collaboration is in the culture. These relationships were already built, largely by having sat down for lunch together for years and discovering shared interests.”

The Chagas inhibitor was the first to come out of this collaboration. Serendipitously, at the same time the drug was under development, UCSF School of Pharmacy alumna Victoria Hale established One World Health, a non-profit pharmaceutical company, which “fills in the gap at the other end” to get this drug distributed to where it’s needed.

Future targets

While they are developing drug targets for the remaining four diseases, the team is also incorporating long-term strategies to develop successive generations of drugs, in anticipation of the resistance that will invariably develop.

Another critical ambition is to set up a fund for scientists from affected countries to come here, to learn techniques to take back with them and to establish long-term liaisons. A Zambian chemist from the University of Capetown, South Africa recently wrapped up just such a sabbatical at UCSF.

McKerrow also dreams of expanding the Center and its capacity to provide a community service for scientists in the field by developing a resource of chemical leads, drug metabolism expertise, and access to high throughput drug screening.

“We want to tell researchers around the world that we're ready to help them take on their targets as well."