MEDICINE / CYSTIC FIBROSIS : Lung Function Improves With Use of Experimental Drug

A genetically engineered drug holds promise as a treatment for cystic fibrosis, according to a preliminary study reported today in the New England Journal of Medicine.

The study of 16 adults found that the experimental drug improved lung function in the short term. But the report did not assess whether the medication, which helps dissolve thick, infected mucus when breathed into the lungs, could enhance long-term survival.

“Within 12 to 24 hours the patients report that they feel better and can do more,” said the study’s senior author, Dr. Ronald G. Crystal of the National Heart, Lung and Blood Institute in Bethesda, Md. The preliminary study “is a significant advance not in curing the disease but in making the lives (of patients) more normal.”

The medication, known as recombinant human deoxyribonuclease 1, or rhDNase, is manufactured by Genentech Inc. of South San Francisco and available only as part of research studies. Crystal has been a paid consultant to Genentech on several subjects, but not the cystic fibrosis project, which was funded by the federal government.

Cystic fibrosis, which primarily afflicts Caucasians, is the most common lethal genetic defect in the United States. Patients typically succumb to chronic progressive lung disease by their late 20s. They are often hospitalized for pneumonia and related ailments. There are an estimated 30,000 to 50,000 cystic fibrosis patients in the United States, Crystal said.

Currently the mainstays of cystic fibrosis treatment are antibiotics and chest physiotherapy, a mechanical pounding on the chest to dislodge secretions so that they can be coughed up.

The secretions of cystic fibrosis patients contain high concentrations of DNA, which forms a thick and sticky substance. The DNA, which is the genetic material contained in cells, is released into the lungs from white blood cells, which accumulate to fight the infections that afflict the patients.

According to Crystal, the rhDNase works as a “molecular scissors” that chops up the thick, infected mucus. After an aerosol treatment, patients are better able to clear their air passages by coughing.

The patients were evaluated while they received rhDNase and while they received a placebo. Different dosages were tested, and patients were typically treated twice a day for a week.

Tests of lung function, which measured the capacity to blow air out of the lungs, typically improved by 10% to 20% as a result of the therapy, the report said. Larger trials of rhDNase involving hundreds of patients are planned.