A small clinical trial of an experimental drug made by Cambridge-based Vertex Pharmaceuticals has successfully targeted the root cause of cystic fibrosis, generating cautious excitement among doctors and patients. Despite the limitations of the study, designed to test the safety of the drug over a short time frame, a number of researchers said the new work represents the most significant advance against the disease since the genetic defect that causes it was discovered in 1989. Although patients' life expectancy has increased over the last two decades, treatments have targeted secondary problems that arise from the faulty gene - vibrating vests that break up mucus in the chest, or antibiotics to fight bacterial infection. The new work is powerful proof that it is possible to treat the underlying problem, and to see modest improvements in lung function, said specialists on the disease. 'The history of cystic fibrosis in this country is one of false starts,' said Dr. Craig Gerard, chief of respiratory diseases at Children's Hospital Boston, who was not involved in the study. 'That's why I use words like 'cautiously optimistic.' ... This is a brand-new treatment that is the first of its kind to affect mechanisms of disease. It proves we're going down the right path.' In the study, 39 people who carried one of the mutations that give rise to cystic fibrosis, accounting for 3 to 4 percent of cases, received the drug or a placebo. The research, partly funded by Vertex and published Wednesday in the New England Journal of Medicine, found that the compound acted directly on the root cause of cystic fibrosis, a protein that ordinarily acts as a channel for transporting salt and water, but malfunctions in cystic fibrosis. To test for cystic fibrosis, doctors look for abnormally high levels of sweat chloride - the amount of salt in the sweat of patients. The drug reduced that, although not to normal levels. It also resulted in modest improvement in lung function. Robert Beall, president of the Cystic Fibrosis Foundation, a nonprofit group that has provided $76 million to support the research, said he was there when the results were first presented to investigators a year ago. 'I saw emotions from those people, those scientists and physicians, that I had never seen,' Beall said. 'They had never seen anything like this before.' Beall added that it is impossible to know how the drug will ultimately fare after more testing. Vertex is testing the compound, VX-770, in a larger study designed to more broadly assess its effectiveness. The company could apply for approval from the US Food and Drug Administration in 2011. Vertex also has a second drug in clinical trials targeted at another mutation carried by 90 percent of cystic fibrosis patients. The company is best known for telaprevir, an experimental drug for hepatitis C that is in late-stage clinical trials, and which analysts expect to be a billion-dollar drug. Cystic fibrosis is a rare, inherited disease that affects about 30,000 people in the United States today. In the disease, the mucus of the lung becomes thick, providing a niche for bacteria to grow and causing damaging inflammation. Patients' average life expectancy is about 37 years. Patients with the disease lose about 2.5 percent of lung function every year, Gerard said, and slowing that decline could have a huge impact on their lives. Michelle Devilly, a sophomore at the University of Massachusetts Dartmouth who was diagnosed with cystic fibrosis at age 5, balances the demands of normal college life with a grueling treatment regimen. Devilly is upbeat but admits that it can be frustrating. She must take a regimen of pills every time she eats, schedule time for therapies that break up mucus in her chest several times a day, and worry about staying healthy. Anything that could make her life more normal would be welcome, but she said she is cautious about the research results. 'To be honest it's like I don't really believe it because I've been doing this for so long,' Devilly said. Beyond its potential for cystic fibrosis patients, the study is also an example of how medicine based on genomics can work. Instead of treating the symptoms or secondary effects of the disease, researchers investigated the effect of a specific genetic mutation - a similar approach to the ones researchers are using as they study genes that play a role in common diseases. But it also shows how finding the gene is only the beginning of the process. The discovery of the cystic fibrosis gene raised hopes that a cure would be found quickly, but it has been two decades. 