A Healthy Gamble for Cystic Fibrosis

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The first challenge for drug development, therefore, was to create a test that would allow researchers to screen drugs that might fix the channel. When Beall called Aurora, later acquired by Vertex, the company was willing to try. It helped that the scientist he called, Paul Negulescu, had done training in a CF lab and had an interest in the disease. Beall agreed to pay the company $2 million to create the needed test.

"A Needle in a Haystack"

Negulescu's team engineered a cell that contained the defective channel and then devised a method for measuring the flow of chloride across its membrane. That meant they could start testing potential drugs, which would require more money. Beall went to the Bill & Melinda Gates Foundation, which provided $20 million for the project, and quickly added $20 million from the Cystic Fibrosis Foundation's coffers, making it possible for Aurora to screen more than 1 million chemicals. "It was a long shot," Negulescu admits. "We were looking for a needle in a haystack."

Many scientists thought that needle might not even exist. They believed the chloride channel was so irrevocably broken that no drug could have an effect. Those naysayers were wrong. True, nothing panned out in the first round of screening. But Negulescu improved the assay, and the team screened the million chemicals again in 2003. This time, they found a few that changed the channel. The scientists then made several thousand variations of the best one, searching for a version that was more potent and better suited to becoming an actual drug. No one knows exactly how the one they ultimately chose works, but "we do know it increases the probability that the channel will be open," Negulescu says.

Hope for Longer Lives

When it came time to begin testing the drug in patients, the researchers faced several challenges, says the University of Colorado's Accurso. While it was easy to see the drug working in the test tube, researchers weren't sure how to determine whether it was working in patients. Accurso's group settled on three indicators: They measured patients' lung function, voltage changes across cells in their noses, and the saltiness of their sweat, which is typically laden with sodium chloride. The results surprised Accurso. "I would have been happy if we had found positive changes in any one of these three things," he says. But all three showed improvement. "It's very exciting. We've never had a treatment that could change the sweat chloride," says Accurso.

If the drug proves to be safe in the long run, those changes "could theoretically add decades to patients' lives," says Beall. It doesn't offer hope to all sufferers, however. The drug may help those patients whose cell walls have a defective channel, but they represent only a minority of CF sufferers. For the majority, the protein the cell produces to create the channel is so defective it never makes it to the membrane in the first place.

Yet there's cause for optimism among these patients as well. "We have a drug that's even more magical," says Vertex CEO Joshua Boger. In the course of screening those million chemicals, Negulescu's team found one that frees up the stuck protein inside the cell, enabling it to make it to the membrane. "The real experiment will be the combination of the two," says Boger.

Carey is a senior correspondent for BusinessWeek in Washington .