New Drug To Treat Cystic Fibrosis

By Margarita Nahapetyan

A new aerosol spray may prove beneficial for cystic fibrosis patients by keeping their airways moist and clear of mucous, which is a key factor in the disease, indicate the new findings by the U.S. scientists.

"Our results suggest that we have identified a new agent that acts directly on a specific pathway, which is involved in the development of cystic fibrosis," said a lead investigator, Dr. Andrew Hirsh, PhD, a senior director of drug discovery and preclinical development for Parion Sciences in Durham, N.C.

In normal respiration, the moist surface of the airway allows individuals to effectively clear mucous, thus keeping airways open and viable. But patients with cystic fibrosis have a genetic defect of ion transport, the hydration level of their airway is changed and the airway mucous starts building up, interfering with normal respiration.

One of the mechanisms that prevents airways from clearing mucous in a proper way is the body's natural homeostasis of sodium, which, when absorbed too quickly from the surface of the airway, causes moisture to become absorbed too quickly. The quick absorption of sodium from the surface of the airways results in their dryness, and allows mucous and bacteria to accumulate.The experts said that the lack of mucous clearance results in chronic infection of a respiratory tract as well as impaired pulmonary (lung) function. As of today there are no therapies available to particularly treat this channel in patients with cystic fibrosis.

The investigators at Parion Sciences, have found that the aerosol-based therapy which was tested during their study, uses a specific epithelial sodium channel-blocking agent called GS-9411, which does not allow sodium to be absorbed across the airway, therefore helping the surface to stay moist. The study was carried out during the pre-clinical stage of development in order to compare GS-9411 to amiloride, an established epithelial sodium channel blocker.

During the experiment, the investigators administered GS-9411 to airway surface cells that had been grown in the lab, and analyzed the effect and reversibility of the drug on these cells. The results revealed that GS-9411 allowed the cells to retain moisture for more than 8 hours. The scientists also discovered that concurrent studies on animals showed that the agent enhanced mucous clearance for more than 4 hours.

According to Dr. Hirsh, the findings offer new hope for those individuals who suffer from cystic fibrosis condition. "The potency and the length of time that the drug was effective in cells and in animal studies was an outstanding feature that distinguishes this compound from other agents," he said.

The clinical phase of the drug development cycle will give the scientists an opportunity to continue to refine the treatment for eventual distribution to patients with cystic fibrosis. GS-9411 administered by aerosol can increase airway surface liquid in a very effective way and enhance the clearance of mucous in an animal model, the authors wrote. The new findings show that GS-9411 warrants further investigation as a new drug therapy to diminish respiratory infection and improve lung function.

The findings were presented on May 17, 2009, during the American Thoracic Society's 105th International Conference in San Diego.