Patients with cystic fibrosis lack a protein called CFTR (cystic fibrosis transmembrane regulator), which is involved in the transport of chloride ions in and out of cells. Without this protein, thick mucus clogs the lungs, eventually leading to respiratory failure. Scientists found that patients given the drug showed protein production in the nasal epithelium, which is similar to the lung epithelium. Patients also wore vests studded with sensors, which indicated a 30 percent reduction in coughing: people with cystic fibrosis cough an average of 600 to 1,500 times a day, compared with two or three times for healthy people. However, neither study was blinded, meaning that both scientists and patients knew who was getting the drug.

A larger, placebo-controlled study of the drug's effectiveness against muscular dystrophy is now under way, with 175 patients at 38 sites in the United States, Europe, Australia, and Israel. A similar study for cystic fibrosis will begin next year. The tests will last a year or more, allowing scientists to determine whether, over time, the drug can boost protein production enough to halt the progression of the diseases. (Even though scientists measured changes in some symptoms in the earlier studies, they were not designed to determine how effective the drug was at treating patients, but rather whether the target proteins were made.) Lee Sweeney, a biologist at the University of Pennsylvania who collaborates with PTC, estimates from animal research that protein production will need to rise to about 20 to 30 percent of normal levels. "We will get insight over the next six months into how much we can halt their disease," he says.

The trials will also be an important test of safety. While no safety problems have yet arisen in human studies, the long-term effects of the drug are not yet clear. "I do worry a bit about off-target effects," says Melissa Spencer, a researcher at the DMD research center at the University of California, Los Angeles, who is not involved with PTC. Because the drug allows protein-production machinery to skip over premature stop signs, there have been concerns that it might skip normal protein termination signals as well, producing extralong proteins. PTC says that so far it has seen no signs of this.

The drug has also shown promise in animal models of other diseases, including Rett syndrome, some tumors with mutations in tumor suppressor genes, and hemophilia, says Stuart Peltz, PTC's chief executive officer. The company is now planning human tests of the drug for hemophilia A and B, he says.

Because the compound is a small molecule that can be taken orally, it has some advantages over other new biological therapies being developed to treat these diseases, including gene therapy and RNA interference. Such therapies are often difficult to deliver and can trigger immune reactions. "It's essentially a gene therapy that is using cellular machinery rather than introducing DNA," says Spencer. "The chance of immune response is much less than if you took a virus and put it in that way."