Jim McKerrow, a University of California, San Francisco, professor, has filed an investigational new drug application with the Food and Drug Administration — without the financial backing of a pharmaceutical company. For 20 years, McKerrow has been trying to find a treatment for Chagas disease — classified as a neglected disease — and has found what he thinks is the best hope of curing it. It's called K777, a compound originally developed for testing against cancer and inflammatory diseases.
When McKerrow first began his research into the Chagas-spreading parasite Trypasonoma cruzi, he was looking for a target that would be susceptible to treatment. He found the protease cruzain, and, through the use of protease inhibitors, showed that if you kill that enzyme, you can kill the parasite. "We would test [the protease inhibitors] against the parasites and it turns out that K777, which was a protease inhibitor, was the best thing we saw in terms of inhibiting the enzyme and killing the parasite," McKerrow says.
In 2005, McKerrow and Steve Barr at the Cornell University School of Veterinary Medicine teamed up and validated the compound in mouse and dog models of cardiac disease. The NIH then funded pre-clinical pharmacokinetic and toxicology studies in dog, primate, and rodent, which were completed late last year, McKerrow says. "Things looked really good, so we submitted the IND," he adds.
McKerrow says that it's rare for a university to independently submit applications to FDA to develop a drug. "In fact, I don't even know of another example where something was discovered and developed entirely outside of industry, which is what's happening here," he says. But it's a necessary change, as most pharma companies are not pursuing Chagas and other neglected diseases, McKerrow says.
He's had to learn a lot about where to get funding. "When the FDA approved us for Phase I trials, they asked, 'Are you going to start this month?'" McKerrow says. "They're used to talking to large companies, but we have to find the money first." McKerrow's lab, the Sandler Center for Basic Research into Parasitic Diseases, submitted a grant application in collaboration with the Drugs for Neglected Diseases Initiative — an international nonprofit that facilitates downstream drug development for neglected diseases, largely funded by the Gates Foundation — and he says he's confident they'll get the money they need to continue the work. "That's the way it works when you're not a company. You don't have stockholders or venture capital supporting you, so you have to turn over every stone [to find funding]," McKerrow says.
He's also hoping to start a trend. "We could do this again and we could do it a lot more efficiently because we know where to turn," he says. "What I'm really hoping is that this will serve as a model for other similar efforts around the world."